LYME SCI: Seeking better treatments for persistent Lyme disease
Targeting persistent Lyme
A new study in mice sheds more light on the question of Lyme disease symptoms that persist after a “standard” course of antibiotic treatment.
These findings from Johns Hopkins University (JHU) may lead to more effective treatment for human patients with persistent Lyme disease symptoms
The study, published March 28 in Discovery Medicine, is the first to look at triple-drug combination antimicrobials in a mouse model. This is a crucial requirement before human clinical trials can begin.
First, some context
In 2017, there were an estimated 427,430 cases of Lyme disease in the United States. Studies have shown that when diagnosed and treated during the early phase of Lyme, 10-20% of patients will fail to improve after a two-to-four week course of standard antibiotics.
These persistent symptoms, which may include brain fog, pain, headache, and fatigue, have been labeled “Post-Treatment Lyme Disease Syndrome” (PTLDS) by the CDC. (Here’s why LymeDisease.org opposes the use of PTLDS as a diagnostic term.)
Patients who are diagnosed after the infection has disseminated (after four weeks or more), have an even greater chance of having persistent or recurring symptoms following standard treatment.
(I’ve previously written about brain inflammation, and small fiber neuropathy found in patients with continuing symptoms after short-term treatment for Lyme disease.)
This new study has two major findings that I will break down in detail. But first, let’s address how Lyme persists, and the hotly debated reasons why so many patients are left with chronic symptoms following treatment for Lyme disease.
How Lyme disease persists
Borrelia burgdorferi (Bb) is the pathogen that causes Lyme disease. In its basic, or growing form, Bb lives as a cork-screw shaped spirochete.
However, when Bb encounters stress—from such factors as the environment, contents of the tick gut, the human (or mammal) immune system, or antibiotics—it will change form. Depending on the type of stress, Bb may turn into round body forms (cysts) or biofilm-like microcolonies. This is known as “pleomorphism.”
Most antibiotics are designed to target bacteria in the growing phase. However, when threatened by antibiotics, Borrelia can simply change to a slow-growing or dormant form.
This also makes it difficult to diagnose Lyme disease via standard blood cultures. Furthermore, the lack of adequate blood tests makes it harder to determine whether the infection has cleared or not.
Many animal studies have shown that Lyme can persist or resurge up to a year after standard antibiotic treatment. It has also been demonstrated in the laboratory that standard antibiotics (doxycycline, Amoxicillin) are effective against the spirochetal (growing) form of Borrelia, but ineffective against the biofilm/persister (pleomorphic) forms.
The authors of the new JHU study have shown that these pleomorphic forms are also “persister cells.” They can cause inflammation and contribute to continuing symptoms in Lyme patients. [I wrote more about “Why persister cells matter with Lyme disease” here.]
Persistent Lyme Disease
There are many reasons why symptoms might persist following standard treatment for Lyme, including:
Co-infections (other bacteria, fungi, parasites, viruses)
Damage caused by the pathogen (especially with late or delayed diagnosis),
Improper or inadequate treatment, and
Autoimmune reaction caused by a failure of the immune system to clear the infection and/or the dead remnants of the infection.
The new study by the JHU research team supports the idea of persistent infection and adds two more possible explanations for persistent Lyme disease (PLD).
Biofilm/persister forms of Borrelia may cause more severe forms of the disease at the onset of illness
Biofilm/persister forms may be able to evade standard antibiotics (e.g. Amoxicillin, doxycycline, ceftriaxone), resulting in treatment failure.
The authors propose dividing patients with PLD into two categories:
Type I. Early development of PLD, due to biofilm/persister forms of the bacteria transmitted from the tick at the beginning of infection. (In mice, the onset of severe disease was seen as early as 9 to 21 days after infection.)
Type II. Late development of PLD, due to initial infection not being diagnosed or treated early. Thus, the infection develops into late persistent disease, with the presence of treatment-resistant biofilm/persister bacteria.
The pleomorphic nature of Borrelia has not gained the attention it deserves in terms of severity of disease and susceptibility to antibiotics. To my knowledge, this is the first mammalian study that separately tests different antibiotics against different forms of Bb. These forms include active spirochetes, (noted as “log phase” in the chart below) and the biofilm/persister form (noted as “MC”).
In this study, researchers grew natural strains of Bb (297 and N40) in the laboratory. Then they separated the bacteria according to pleomorphic form. (See Log phase Bb and MC Bb in table below.) Finally, they injected each of the Bb forms into two separate groups of laboratory mice.
The mice were further separated into sub-groups of five. Researchers then treated each sub-group with a different antibiotic or combination of antibiotics for 30 days as follows: Saline, doxycycline (Dox), ceftriaxone (CefT), Dox+Ceft, vancomycin (Van), Van+CefT or Doxy+CefT+Daptomycin (Dap). The mice were then monitored for an additional 60 days for any relapse and persistent infection.
More at this link: https://www.lymedisease.org/lymesci-jhu-persistent-lyme/?