This is part 1 of series on persistent lyme disease.
Read Part 2: Addressing Biotoxins in Persistent Lyme Disease
Why Doxycycline Works….Initially
If you knew a tick had bitten you, and you developed the bull’s-eye rash and a flu-like malaise later that week, and you were aware that this meant Lyme disease, you’d see a doctor to start an antibiotic. The doctor who greets you should know enough to prescribe Doxycycline. The most common approach to treating acute Lyme disease relies on Doxy alone. Those who follow the guidelines of the Infectious Disease Society of America (IDSA) recommend two weeks on Doxy. The International Lyme and Associated Diseases Society (ILADS) recommends using Doxy for 6 weeks.
Doxy has the ability to disable Lyme spirochetes. The most common Lyme spirochete is known as Borrelia burgdorferi, or Bb. Your immune system has an easier time dispensing with disabled spirochetes compared to the more difficult task of hunting down fully functional, immune evasive spirochetes. Doxy amplifies your immune response against Lyme spirochetes. As a result, you are likely to feel worse for several days after starting the Doxy. You’ll start to feel better within a week or two as your immune system quiets down.
Doxycycline Doesn’t Kill All Forms of Borrelia
Does that mean you were cured of acute Lyme disease? Hmm. Research clearly shows that Bb is pleomorphic. This means that Bb has more than one morph, or physical form. Bb is known for its squiggly spirochete form but it can shift into what’s called a round body form. A Lyme round body consists of 6 to 12 spirochetes rolled up together, surrounded by a phospholipid membranes. Many use the term “cystic form” but this is less accurate because the outer membrane of a cyst is not composed of phospholipids.
The 6 to 12 Bb spirochetes inside a round body are not metabolically active. Without metabolic activity such as protein synthesis or self-replication, there is nothing for an antibiotic to disrupt. Despite being in a state of suspended animation, round body Bb spirochetes remain viable by mooching nutrition from their surroundings. We suspect that they are engaging in the passive transfer of genes, as if they were Pokemon cards, each conferring a unique form of defense against you, their host.
In this round body state Bb tolerates the vast majority of antibiotics. So what if your Doxy led attack against Bb induced groups of spirochetes to morph into their round body form? You’d feel better because the round body forms are too inactive to cause inflammation. Their phospholipids membrane renders them virtually invisible to your immune system. No inflammation, no symptoms. In other words, we cannot be sure that we have beaten your Lyme infection into submission by using Doxy alone.
Post-Treatment Lyme Disease Syndrome
A few months may pass, but the Bb that survived the Doxy attack by hiding within round bodies may reactivate. Some of the reactivated Bb may draw the attention of your immune system so there could be bouts of inflammation and symptoms to go with them. Your joints could start to feel painful and stiff. Your heart could race and skip beats now and then. You might find that you have trouble staying focused on your work along with short-term recall or word finding problems. You might grow increasingly irritable and all of a sudden notice that you’re unusually sensitive to bright lights and harsh sounds. Then you might notice that you’re sleeping poorly, tired most of the time, that your neck hurts, and that there’s something wrong with your vision.
You could very well have post-treatment Lyme disease syndrome, or PTLDS, not because your course of Doxy was too short but because treatment took aim only at Bb’s spirochete form with no attention paid to the round body form. This strategic error would allow enough Bb spirochetes to duck and cover as round bodies and ride out the Doxy storm only to reactivate months later in numbers high enough to cause irritation and inflammation in multiple tissue sites. In my opinion, the treatment of acute and persistent Lyme should include an antibiotic that can kill or disable the spirochete form plus an antibiotic that can kill or disable the metabolically inactive round bodies. We can end its game of hide and seek.
Combination of Antibiotics to Beat Lyme Into Submission
Any antibiotic strategy against Lyme disease that relies on a single antibiotic makes no sense. What makes sense is to use one antibiotic that is able to kill or disable metabolically active Bb. This antibiotic could be from the penicillin, cephalosporin, tetracycline, or erythromycin class and would be used to “patrol the streets.”
The second antibiotic should be used to “beat the bushes” for round bodies. Any round body Bb able to escape such and antibiotic would theoretically get caught in the dragnet set up by the antibiotic being used to patrol the streets.
Three antibiotics have been shown to work against the metabolically inactive round body form of Bb. They are:
1. Metronidazole (Flagyl)
2. Tinidazole (Tindamax, or Tindy for short)
3. Cefuroxime (Ceftin)
Based on a study from the University of New Haven (Sapi, 2011), Tindy does the best job of killing viable Bb in the lone spirochete and round body form. Ceftin was recently shown to have strong activity against both forms in a study from Johns Hopkins (Feng, 2014).
We know how Flagyl and Tindy work. They track to bacterial DNA and disable it via nitrosative stress. It’s not clear how cefuroxime disrupts metabolically inactive spirochetes in a dish, let alone in a living system, but based on the Hopkins study it may, like Tindy, be a dual-purpose antibiotic that is able to cover both lone spirochetes and round body forms. This would depend on how well Ceftin can penetrate living cells and tissues in search of round bodies.
In my experience, people have a harder time tolerating Flagyl than any other antibiotic used to treat Lyme disease. Maybe that’s why they called it Flagyl–because it flagellates people. I like to spare my patients the misery that Flagyl can cause. On the other hand, my experience with Tindy is promising.
In my practice roughly 70% of patients with suspected PTLDS experience a Jarisch-Herxheimer reaction the day after they have taken Tindy. The remaining 30% Herx the day they take it, two days later, three days later, or don’t Herx at all. The latter event reduces my suspicion of PTLDS as a viable diagnosis. This is because Herxing on Tindy indicates that it is showing the immune system where the round body action is. This is supported by the observation that cessation of Herxing on the higher dose of Tindy correlates with a substantial reduction in symptoms.
Because Tindy is heavy duty and can cause neuropathy I pulse it twice a week. I also let the patient pick which days. It doesn’t hurt to vary the schedule. Once the patient determines his or her pattern of Herxing on the Tindy, they can adjust the schedule to avoid Herxing on a day when the patient can’t risk being impaired. Herx moderation strategies help in most cases. By using Tindy to beat the bushes for round body forms twice a week, and monitoring the onset, duration, and strength of the Herxing it causes, we get an idea as to whether our antibiotic combination is beating Bb into submission.
A Realistic Goal for Treatment
We know from studies on healthy mice that Bb can reactivate in response to a feeding tick (Hodzic, 2014) and to immune suppression (Yrjanainen, 2008). Exactly what degree and form of immune suppression is required to reactivate round body or persister forms of Bb remains to be seen. It may be that the most realistic goal of treatment for Lyme disease is to kill or disable as many Bb as possible so that any spirochetes left in the body are metabolically inactive and therefore not causing inflammation. The goal of eradication is less realistic given the immune evasive and persistence abilities of Bb. Besides, we have no methodology for proving eradication of Bb.
Granted, it is a challenge to reassure patients that beating Lyme into submission is a “win.” The thought of viable spirochetes in suspended animation isn’t exactly comforting. When Herxing ceases on the 500 mg dose of Tindy it is time to talk about stopping the antibiotics. I prepare the patient by pointing out that symptoms may occur in the first three days or so off of antibiotics. These symptoms are produced by pathways having to adjust to the absence of the antibiotics that have been present for several months (typically 3 to 9 months).
I explain that nature likely would not select a mechanism for an immune evasive species like Bb that would have it poke it’s head above the wall the very first day that a months-long antibiotic attack ceases fire. The antibiotic withdrawal phenomenon happens early and ends quickly. Metabolically active Bb may replicate at varied intervals, the slowest being about 6 weeks. So if the patient makes it 6 weeks off antibiotics without symptoms we infer that whatever Bb remain are metabolically inactive and that we’ve beaten Lyme into submission. Should symptoms recur at some later date, they should not be severe and should respond to a much shorter course of a common sense antibiotic combination.
Keith Berndtson MD is the medical director of Park Ridge Multimed and a leading midwestern resource for patients who have, or may have, Lyme disease. Read his entire bio here.