Friday, April 26, 2019

Zhang's mice. And, where have all he patients gone? The cure!


Lyme cured! Or is it. Dr. Zhang and (Jie Feng) are heroes in the Lyme story and their work will be of great import in the history of medicine.

Dr. Zhang and colleagues have been very busy building the case for chronic Lyme disease or persistent Lyme disease. Their publication March 28, 2018 support previous in-vitro (test tube) studies in a mouse, called a “murine model.” He has previously demonstrated that Borrelia burgdorferi strains, bacteria responsible for Lyme disease subdivide into different morphological forms. The means the same bacteria, with the same DNA, can alter their appearance and function dramatically. We associate a thin spiral, elongated form with Lyme, a spirochete. But the long thin forms of Lyme can change shape and appear round. Alternatively, the spirochetes can aggregate in a community protected by strong mucopolysaccharide substance, a microcolony or biofilm.

Three forms:  spirochetes, round forms and microcolonies (biofilm colonies).

The bacteria can be free floating in the blood referred to as planktonic forms. The term contrasts bacteria safely guarded in the biofilm (microcolony) form. I have always thought of planktonic bacteria as free swimmers. They are demonstrated to be primarily round form and non-motile in the studies.

Test tube finding (in-vitro) support the mouse study.

The different forms, morphologies Lyme takes on are best killed by different antibiotics. Only a specific combination of three antibiotics eradicates Lyme spirochetes in mice infected with microcolonies.

Posttreatment Lyme or persistent/recurrent symptoms may occur in 20% of patients treated by standard protocols, generally with doxycycline. (This is from the CDC). A study from 2015 indicates that 36-63% of patients may have persistent symptoms.

The term PTLDS, posttreatment Lyme disease syndrome is popular but not helpful.  I believe its use is primarily political, used in deference to the powers that be.

PTLDS ostensibly describes a group of patients with early diagnosis and treatment who nonetheless develop chronic symptoms.

The authors brilliantly point out that there exists a large population that never receive early diagnosis or treatment which he refers to as type 2 patients.  In my experience most patients are type 2.

Experimentally, spirochetes were divided into the three forms through laboratory procedures. 

Mice were inoculated with either spirochete or persister forms.

Pathologists examined tissues for inflammation. The  greatest was observed in mice infected with persister forms, especially biofilm forms.

Mice infected only with spirochetes could be cured with doxycycline and other antibiotics.

Mice infected with stationary forms were only cured with the specific combinations of: Daptomycin, Ceftriaxone and doxycycline. Negative cultures were obtained from  ear biopsy and bladder tissues.

The authors suggest that different forms of Lyme are delivered through the tick bite. Biofilm colonies may be introduced in tick saliva and then seed other tissues.

This is contrary to what I know about the bacteria.  Lyme bacteria are highly motile, extracellular and possess ligands which facilitate adhesion to the matrix between cells. The bacteria are polytropic or pantropic and quickly infect many tissues and organs. There is no known mechanism by which biofilms can directly seed other tissues. The standard model is that organisms within a biofilm communicate by molecular signaling, quorum sensing-- and that individual, planktonic spirochetes are released under the right conditions to seed new tissues and create new biofilm colonies.  The spirochetes may be protected by special compartments in the body, for example they readily cross the blood brain barrier and live in the brain, an immune privileged area. Biofilms have been demonstrated in the brain. I think only individual spirochetes with their lipophilic outer membrane can get through the blood brain barrier.

There is ample evidence that spirochete rapidly convert to round forms when attacked by antibiotics. In-vitro colonies of spirochetes morph into other forms, persister forms, the 5% doxycycline does not kill.

If biofilm colonies are truly injected into skin by ticks at the outset, standard therapy, doxycycline and others is doomed to fail.  Very plausible. Frightening. 

The currently recommended therapy for early, stage 1 Lyme disease is a failure. It might be argued that other regimens should not be experimented with. These new therapies have no scientific basis. But there is compelling scientific evidence that standard therapy is a failure.  

Oral therapies with combinations that showed some promise invitro might have a better chance, for example, doxycycline, rifampin and artemisinin.

The curative therapy described is problematic. Ceftriaxone and doxycycline are standard, generic fare but not daptomycin. Daptomycin is a relatively new, powerful antibiotic currently held in reserve for multi-resistant bacteria such as MRSA.  It’s non-generic cost of $400.00 per dose/day-- not covered by insurance may be prohibitive. A thirty-day course costs $12,000. Generic available, $150.00 per dose. Cost lowered to about $4000.00 monthly.

Experimental treatment based on scientific plausibility and clinical experience for late stage Lyme has helped many, many patients.

The paradigm that Lyme disease present with: an observed tick bite, a bull’s eye rash, Bell’s palsy, a swollen knee, meningitis, heart block and other well described acute manifestation is wrong.

Ticks go unseen, rashes are the exception not the rule and most patients present with -- fatigue, pain, neurological symptoms and cognitive dysfunction – the bones of Lyme disease. The meat is filled with symptoms referable to nearly every organ system. Most patients go misdiagnosed for months, years or decades. This is the tragedy of the Lyme epidemic.

Patients are belittled, diagnosed with chronic fatigue syndrome, fibromyalgia, depression and/or the aches of pains of daily living.

Doctors who take chronic Lyme seriously are ridiculed by peers and medical licenses are censured.

There is math problem

Of 300,00 type 1 Lyme cases yearly in the U.S. 60,000 become chronically ill.  The number is at least doubled when you add in type 2 cases.

This means there must be hundreds of thousands of patients, more likely  not millions of patients suffering with chronic Lyme disease.

Despite this patient are nearly universally told it’s not Lyme, can’t be Lyme, no known disease acts like that, etc.

This leaves a simple question: Where are all the missing patients?

Einstein warned scientist lack imagination. Everything doctors do today with be laughable to future counterparts. Phages which kill only specific bacteria or other technologies will surely make antibiotics obsolete in the not too distant future.

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Alex said...
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