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.
New And Promising Research On Lyme Disease
Current research seeks to address big holes in our understanding of Lyme disease and PTLDS: Why do symptoms persist? Are bacteria hiding in the body? Can we detect Lyme infection earlier to better use antibiotic treatment?
The results of clinical studies are described throughout this article, and you may wonder which treatments are worth discussing with your doctor. When a particular benefit is described in only one or two studies, consider it of possible interest and perhaps worth discussing, but definitely not conclusive. Repetition is how the scientific community polices itself and verifies that a particular treatment is of value. When benefits can be reproduced by multiple investigators, they are more likely to be real and meaningful. Weve tried to focus on review articles and meta-analyses that take all the available results into account these are more likely to give us a comprehensive evaluation of a particular subject. Of course, there can be flaws in research, and if by chance all of the clinical studies on a particular therapy are flawedfor example with insufficient randomization or lacking a control groupthen reviews and meta-analyses based on these studies will be flawed. But in general, its a compelling sign when research results can be repeated.
Shedding Peptidoglycan And Arthritis
Finally, a likely explanation for some of the persistent symptoms in PTLDS. Brandon Jutras, PhD, and colleagues have found that B. burgdorferi sheds something called a peptidoglycan, and theyve shown that this molecule persists in the joints of people with Lyme arthritis. They also found evidence that the body mounts an immune response to this foreign moleculethey found antibodies and inflammatory moleculesand that this response is likely responsible for pain and inflammation. Peptidoglycan sticking around even after the bacteria are eradicated could explain the arthritis that persists in 10 percent of cases, even after treatment with antibiotics for two to three months and no evidence of live bacteria . Now we need to discover a way to break down this peptidoglycan.
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How Is Lyme Disease Diagnosed
Diagnosing Lyme disease can be difficult as symptoms vary from person to person. Symptoms can also be similar to other illnesses.
A diagnosis of Lyme disease is based on:
- the outcome of laboratory testing
Laboratory testing may be recommended for patients with signs, symptoms and history of exposure to tick bite to support a clinical diagnosis.
Seek your health care provider right away if you develop symptoms of Lyme disease after being bitten by a tick or if you visited a known at risk area for Lyme disease. The earlier a diagnosis is made, the greater the chance of a successful treatment.
Treating Lyme Disease While Pregnant
Treatment for pregnant women with Lyme disease is similar to that of non-pregnant adults. However, certain antibiotics, such as doxycycline should not be used as it can affect your unborn child.
Research shows that there are no life-threatening effects on the child when a pregnant woman receives appropriate antibiotic treatment for Lyme disease.
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Testing For Lyme Disease In Dogs
Lyme disease spread by ticks can be diagnosed with a simple blood tests in your veterinarian’s clinic. The C6 test is very sensitive and specific at diagnosing cases of Lyme disease and depending on clinical signs and concurrent results, treatment may be started immediately. If treatment has been successful, reductions in the QC6 at six months should be lower than the starting point.
The Rife Machine To Kill Microbes
Can a machine generate radio frequencies that kill borrelia? In the 1920s and 30s Royal Raymond Rife invented a microscope that he claimed could see small viruses that cause disease, and he invented a machine that he claimed used radio waves to vibrate viruses at a mortal oscillatory rate in order to kill them . However, no one has been able to reproduce or validate these reports, and there is no documented evidence for these claims .
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History And Physical Examination
The clinical diagnosis of Lyme disease can be straightforward in patients with a history of tick exposure and the characteristic finding of an erythema migrans rash.12 The CDC has defined erythema migrans rash as an expanding red macule or papule that must reach at least 5 cm in size .11 According to the Infectious Diseases Society of America guidelines, erythema migrans rash is the only clinical manifestation sufficient to make the diagnosis of Lyme disease in the absence of laboratory confirmation.20 Although one study concluded that primary care physicians in a Lyme diseaseendemic area of France correctly identified erythema migrans in 72 percent of patients,22 the study was limited by lack of complete clinical information for the participants.
A number of conditions resemble erythema migrans however, the rapid and prolonged expansion of an erythematous lesion is unique to erythema migrans.11 Lesions most often occur at anatomic sites that are unusual for cellulitis and other conditions that mimic erythema migrans therefore, a complete skin examination should be performed before excluding erythema migrans.20
Detecting Lyme In Hiding
Since borrelia flourishes in ticks, why not see if ticks can be used to find live spirochetes hiding in people? A bizarre new way to look for infection, xenodiagnosis, seems like it might be a possibility. This technique consists of placing uninfected ticks on peoples arms, letting them feed for a few days, removing them, and seeing if they now contain live borrelia. In a small pilot study of sixteen people with PTLDS, one tick acquired B. burgdorferi DNA from a persons blood. That doesnt unequivocally prove that the person was still infected because the ticks could be taking up bits of DNA from leftover dead bacteria. A confirmation would require taking that tick, putting it on a mouse, and that mouse becoming infected. This was not the case for the one positive tickit was not infectious .
A larger clinical study will follow up on these findings. Under the direction of Adriana Marques, MD, at the National Institute of Allergy and Infectious Diseases , researchers will put clean, laboratory-bred ticks on people, let them feed, remove the ticks, and test them for B. burgdorferi. Theyll see how often they find the bacteria hiding in people who have been treated with antibiotics for Lyme.
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What To Expect At Home
Home care for dogs with Lyme disease is relatively straightforward. Doxycycline is usually given by mouth twice daily for at least 30 days. Improvement in the dogs symptoms should be noted within 24-48 hours. If the dogs condition fails to improve in 72 hours or worsens at any time, call your veterinarian.
How Can Lyme Disease Be Prevented
Unfortunately, there is currently no vaccine for Lyme disease. But you can avoid Lyme disease by avoiding tick bites, checking for ticks, and removing ticks promptly, before they become lodged in the skin. Some tips:
Avoid tick playgrounds: Ticks like low-level shrubs and grasses, particularly at the edges of wooded areas. If youre hiking, try to stay in the center of the trail and avoid bushwhacking. Walk on cleared paths or pavement through wooded areas and fields when possible.
Dress appropriately: Long pants with legs tucked into socks and closed-toed shoes will help keep ticks away from skin. Light-colored clothing helps make ticks visible.
Insect repellant: Products that contain DEET repel ticks but do not kill them and are not 100 percent effective. Use a brand of insect repellent that is designated as child-safe if your child is 1 year or older. For infants, check with your pediatrician about what brands are safe to use. You can also treat clothing with a product that contains permethrin, which is known to kill ticks on contact.
Shower after outdoor activities are done for the day. It may take four to six hours for ticks to attach firmly to skin. Showering will help remove unattached ticks.
- all parts of the body that bend: behind the knees, between fingers and toes, underarms and groin
- other areas where ticks are commonly found: belly button, in and behind the ears, neck, hairline, and top of the head
- anywhere clothing presses on the skin
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How Lyme Disease Is Diagnosed
One thing that makes Lyme disease so frustrating is that its diagnosis is not simple. You may be asked if you saw a tick, and if not, your concerns may be dismissed. On the other hand, if you saw a tick and removed it right away, your concerns may also be dismissed because many experts believe the tick has to remain attached for at least thirty-six hours to transmit the bacteria. But if a tick has already partially fed elsewhere, it may be able to infect you in less than thirty-six hours . Be aware that there are other tick-borne diseases, and some can be transmitted in as little as fifteen minutes, as discussed in the conventional treatments section of this article.
A Reasonable Approach To Post
If you are being treated for PTLD, there is no magic bullet to treat this problem, but here are some important steps to consider:
- Choose a doctor you trust and who can work closely with you.
- If your doctor agrees to start antibiotics for several months, make sure you talk about the risks and cost, as this can be dangerous and expensive.
- Make sure not to rely solely on antibiotics. The evidence for a benefit from antibiotics is weak, and we rely mostly on physicians clinical experience and interest in the disease to design a personalized therapeutic plan. For some, a more holistic approach may be the way to go.
- If you try supplements, ask about their source and purity, as they are not FDA-regulated.
- Consider looking for services in medical school hospitals or clinics where they may have programs with ongoing research on how to diagnose and treat Lyme.
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Hunting For Alternative Drug
Frustrated by the lack of treatment options for Lyme disease patients with lingering symptoms, Rajadas and his team began hunting for a better alternative in 2011. In 2016, they published a study in Drug Design, Development and Therapy that listed 20 chemical compounds, from about 4,000, that were most effective at killing the infection in mice. All 20 had been approved by the Food and Drug Administration for various uses. One, for instance, is used to treat alcohol abuse disorder.
Jayakumar Rajadas
In this most recent study, azlocillin, one of the top-20 contenders, was shown to eclipse a total of 7,450 compounds because it is more effective in killing B. burgdorferi and causes fewer side effects. Lyme disease affects more than 300,000 people annually, according to the Centers for Disease Control and Prevention. It can affect various organs, including the brain, skin, heart, joints and nervous system, and cause heart problems and arthritis if untreated. Symptoms include fever, headaches, chills, and muscle and joint pain.
Traditional antibiotics, such as doxycycline, are effective as an early course of treatment for the infection in the majority of patients, but it remains unclear why these drugs fail to treat 10% to 20% of patients, Rajadas said.
Lyme Disease: Resolving The Lyme Wars
- By , Contributor
Its finally getting warm here in New England, and most of us have plans to enjoy the beautiful weather. And thats why the Centers for Disease Control and Prevention recently released a report raising awareness about how to prevent the tickborne infections that typically occur during this time of the year. Lyme disease is probably the most well-known, and the one for which diagnosis and treatment are most controversial.
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Tryptophan For Mood Support
Tryptophan is an amino acid, and like most amino acids, its a building block for proteins. But tryptophan is also used to make the mood-regulating neurotransmitter serotonin. Tryptophan metabolism appears to be altered in Lyme disease, as in other infections , and it has been suggested that tryptophan supplements could be helpful in supporting serotonin production and mood in people with Lyme disease. Taking tryptophan supplements and supplements of other building blocks for neurotransmitters, such as tyrosine and choline, has been proposed for many conditions where the brain is not working optimally. It isnt easy to eat enough supplementary amino acids to affect brain neurotransmitters significantly because neurons tightly regulate the amount of neurotransmitters they make. But there is some evidence that the activated form of tryptophan, 5-HTP, may help support mood regulation . There is not yet evidence of efficacy in treating Lyme disease.
Antibiotic Treatment Of Lyme Carditis
Table 1. Mild
| Age Category | |||
|---|---|---|---|
| 100 mg, twice per day orally | N/A | ||
| 500 mg, three times per day orally | N/A | ||
| 500 mg, twice per day orally | N/A | ||
| 4.4 mg/kg per day orally, divided into 2 doses | 100 mg per dose | ||
| 50 mg/kg per day orally, divided into 3 doses | 500 mg per dose | ||
| 30 mg/kg per day orally, divided into 2 doses | 500 mg per dose | 14-21 | 3 |
Table 2. Severe *
| Age Category | |||
|---|---|---|---|
| 2 grams intravenously, once a day* | N/A | ||
| 5075 mg/kg intravenously, once a day* | 2 grams per day | 1421 | 3 5 12 |
*After resolution of symptoms and high-grade AV block, consider transitioning to oral antibiotics to complete treatment course .
Tissue sample from a patient who died of Lyme carditis. Image taken using Warthin-Starry stain at 158X.
The heart on the top shows how an electrical signal flows from the atrioventricular node to the chambers in the lower half of the heart, called the ventricles.
The heart on the bottom shows a case of third degree heart block. In this illustration, the electrical signal from the AV node to the ventricle is completely blocked. When this happens, the electrical signal of the atria does not transmit to the ventricles , which causes the ventricles to beat at their own, slower rate.
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Different Drugs For Different Bacterial Shapes
Humans apparently arent the only species to show our worst selves when we are under stress. B. burgdorferi, the major bacterial species responsible for Lyme disease, can change its shape when stressed, morphing from its spiral shape into round bodies or into a sticky layer of bacteria called a biofilm. In mice at least, these variants caused more-severe arthritis than the usual unstressed bacteria. They were also more resistant to antibiotics, requiring a cocktail of three antibiotics for eradication. Jie Feng, PhD, and colleagues at Johns Hopkins hypothesize that the success of antibiotic treatment in humans may depend on the variants that a tick injects into you .
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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Treatment For Erythema Migrans
People treated with appropriate antibiotics in the early stages of Lyme disease usually recover rapidly and completely. Early diagnosis and proper antibiotic treatment of Lyme disease can help prevent late Lyme disease.
Treatment regimens listed in the following table are for the erythema migrans rash, the most common manifestation of early Lyme disease. These regimens may need to be adjusted depending on a persons age, medical history, underlying health conditions, pregnancy status, or allergies. Consult an infectious disease specialist regarding individual patient treatment decisions.
| Age Category | |
|---|---|
| 100 mg, twice per day orally | N/A |
| 500 mg, three times per day orally | N/A |
| 500 mg, twice per day orally | N/A |
| 4.4 mg/kg per day orally, divided into 2 doses | 100 mg per dose |
| 50 mg/kg per day orally, divided into 3 doses | 500 mg per dose |
| 30 mg/kg per day orally, divided into 2 doses | 500 mg per dose |
*When different durations of antibiotics are shown to be effective for the treatment of Lyme disease, the shorter duration is preferred to minimize unnecessary antibiotics that might result in adverse effects, including infectious diarrhea and antimicrobial resistance.
NOTE: For people intolerant of amoxicillin, doxycycline, and cefuroxime, the macrolide azithromycin may be used, although it is less effective. People treated with azithromycin should be closely monitored to ensure that symptoms resolve.
