Thursday, July 18, 2019

Novel drugs for Lyme


The dry spell is over. We have some promising new therapies.

Investigators have been used a method to screen large numbers of drugs which might treat Lyme. Dr. Lewis has apparently found that disulfiram, Antabuse, used to treat alcoholics and makes them vomit if they drink alcohol seems to kill Lyme. Apparently, he has discussed his findings at lectures. Practicing doctors don’t get the low down until findings are published in a journal. A recent case report of 3 patients showed efficacy of the drug.  Antabuse is something I have used throughout a 37-year career in medicine. It is generally safe, but liver tests need to be monitored. Repurposing the drug empirically seems quite reasonable. Dr. Fallon, Columbia University, is doing a clinical study. 

The fact that Antabuse is not an antibiotic is exciting.

The combination of Rocephin, doxycycline and daptomycin may be effective in humans. A clinical question is how long do the drugs need to be given?  Will we see durable benefits in 30 days, 60 days etc.?  Can an intensive IV therapy circumvent months, even years of other complex and perhaps less effective therapies? Let’s find out.

Controlled clinical trials are important. Placebos are incredibly effective. Personal interactions influence outcomes as do other confounding variables.  Studying a complex disease like Lyme is challenging; coinfections are not accounted for and a million other variables are not and perhaps cannot be taken into account.. Study results must be interpreted with care, nuance and ample discussion. The limitations of the study must be addressed. And I hope investigators will not be strong armed by politically motivated institutions to parse words when stating conclusions.  These few words have been misinterpreted, willfully with far reaching ramifications. The IDSA drew incorrect and absurd conclusions from Fallon's last Lyme study. And here we go with another set of IDSA recommendations.

Tafenoquine in the form of Krintafel is being used for treatment resistant Babesia. Looks good so far.

Friday, June 28, 2019

Bartonella persisters and daptomycin: two for the price of one?


While Lyme persistence I denied for political reasons the persistence of other human zoonotic pathogens is recognized. 

I have seen two cases of brucellosis recently and Brucella is recognized as a persistent bacterium, perhaps impossible to eradicate, at least with currently used and/or recommended therapy.

B. abortus is one of several well-known human pathogens of the genus, the one which may be acquired via tick bites.

Brucellosis can be acquired by consumption of uncooked meat and raw milk. I don’t understand the fad of drinking unpasteurized milk, a potentially deadly fad.

Brucellosis may cause numerous untoward clinical syndromes many of which similar to those seen with chronic Lyme.

Bartonella, especially B. henselae is a well known tickborne pathogen also known to exhibit persistence. The bacteria, a fastidious (difficult to culture) gram negative rod is an obligate (facultative) intracellular gram-negative bacteria associated with well described clinical syndromes, discussed elsewhere. Spotty medical literature supports the notion that Bartonella infection is clinically persistent.

Biologically, Bartonella are the only bacteria which may reside in red blood cells. The only other RBC pathogens are malaria and babesia species. Specific biological features, a protected niche and the discovery of stationary forms provide an ample narrative of fact and biological plausibility for persistence. 

The primary home for these bacteria is not RBCs but the endothelial cells that line blood vessels. This is why bartonellosis causes well known vasculitis syndromes. 

Zhang, a prolific publisher, should now be a star at JHH published about Bartonella persisters in antibiotics April. Again, daptomycin is the star.   Daptomycin has the best activity against stationary (persister) forms. Only aminoglycosides, e.g gentamycin are competitive.  In my experience, gentamycin may eradicate clinical infection, but not consistently. Complex multidrug regimens are frequently recommended for Bartonellosis, perhaps this is unnecessary.

This study added to others vis-à-vis Lyme raises the clinical (preclinical) question. Should patients with chronic illness caused by Lyme and Bartonella be treated with combination IV therapy, Rocephin, Doxycycline and Daptomycin earlier rather than later in the course of treatment?

From an Evidenced Based Medicine approach this is anathema,  such therapies can only be recommended after randomized clinical trials, peer reviewed and published.

Such studies are perhaps decades away.  Currently the political divide make diagnosis of Lyme nearly impossible, let alone coinfections.

The preclinical approach allows for empiric use of the therapy without waiting for IDSA approval, which may or may not ever come.

This concept of applying preclinical data (translational medicine) is well developed and well used in the field of oncology. Of course, cancer is considered a serious disease (and Lyme isn’t?).

Those of us in the alternative universe of Lyme disease are accustomed to very long-term antibiotics, including IV ones.  In this world, the use of these 3 IV drugs sounds reasonable. In the other world we are no strangers to cocktail therapy and IV therapy.  In the IDSA/CDC world of doxy for 3 weeks even discussion of this idea is heresy or treasonous, if such things apply in medicine (apparently, they do).

Treating chronic Lyme through the other world approach is very complicated, lengthy and expensive. This sort of preclinical information should be considered in lengthy, informed consent discussions with patients.  

Monday, June 24, 2019

Lyme arthritis, peptidoglycans and political correctness




Medical science and other branches of science are biased and political.  A researcher, an investigator(s) has to walk on eggshells when their findings bump up against beliefs of mainstream beliefs espoused by the experts. They have to fall in line with political correctness if they hope to see their research published, and if they want to keep their jobs as academic researchers. .  

The research findings published in the PNAS, Proceedings of the National Academy of Science this month entitled Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis appears to be excellent science.

The research moves the ball forward in our understanding of chronic inflammation associated with Lyme disease. Political correctness and conformity with mainstream thinking corrupts the paper from the start seriously damaging the credibility of the authors.  Immediately the terms postinfectious Lyme arthritis and posttreatment Lyme disease are used and they poison the broth.

The preponderance of scientific evidence, overwhelming and mounting evidence supports the understanding that Lyme bacteria persist in the face of the standard antibiotic therapies discussed.

The finding that peptidoglycan (PPG), the crosslinking molecules which comprise cell walls in gram-negative and gram-positive bacteria are a major determinant of persistent Lyme arthritis is new information that moves the ball forward.

Borrelia spirochetes have a double outer membrane and lack PG cell walls. However, PG molecules are present internally, inside the outer membrane (cell envelope) providing support to the spirochetes.

The fragments of PG are call muropeptides.

We learn Bb, Lyme processes a unique PG structure. And we learn these fragments are highly immunogenic – incite an excessive immune response or cytokine response likely responsible for clinical manifestations of Lyme arthritis.

Perhaps the peptide fragments do cause an autoimmune response. Although the theory is discussed at length this is not what the research shows. Lyme related joint inflammation is directly caused by unique Lyme PGs.  


A variety of experiments, controlled experiments using a variety of bacteria with different PGs, a variety of clinical diagnoses, mice, humans, joint fluid and serum support the findings. The findings are based on a great deal of animal and human research.

Antibodies were developed against Lyme specific PGs. These antibodies could be the basis for a new, more accurate diagnostic test.

From recent research we know that Lyme biofilms and planktonic round forms cause more inflammation than spirochete forms. We know these are the most antibiotic tolerant forms or resistant forms.

The article at length discusses issues related to diminished bacterial recycling of PGs compared with gram negative bacteria.

Two theories are proffered as to how Lyme PG persists after “curative therapy” with a short course of doxycycline or Rocephin. The authors suggest that these mechanisms account for the persistence of symptoms lasting weeks or months.

But Lyme arthritis lasts for years. Biofilm forms are impervious to standard antibiotic therapies.

Somehow the authors suggest that immune suppressive therapy should be considered rather than additional antibiotics.

We have heard catchy phrases like “persistence of evidence or evidence of persistence." The issue has prevsiously be settled.

Good science can easily self-destruct with the unforced errors all for the sake of political correctness.

To bad.

Thursday, June 6, 2019

Lyme, Alzheimer's, Enbrel -- new potential treatment

I have learned that most people want a simple sound bite answer or conclusion. The edges of medicine always operate in the grey and nuanced.

It has long been dogma in Lyme circles that immune suppressing drugs, e.g. Enbrel are very dangerous and should not be used.  The same is true with prednisone.

I have patients who get the occasional injection by their rheumatologist; joint pain gets better and they are no worse for the wear.

The drug is used for psoriasis amongst other many other conditions. The drug has serious side effects: its use should not be taken lightly.

A study suppressed by Pfizer, brought to light be the Washington Post, was based on insurance company data considering outcomes of  hundreds of thousands of patients and found those taking Enbrel had a 64% decrease in the incidence of Alzheimer's disease. 

Enbrel impairs the function of TNF alpha, a master cytokine responsible for trafficking immune cells.

Pfizer did not make the disclosure because: a generic version will be  available.  A shiny new, me-too drug promoted heavily by pharm reps costing obscene amounts of money will take its place. Doctors will be given shiny data, along with lunch, proving equivalency? with the old drug.

The myth that generics are poor (dangerous) and lack quality control may be resurrected.

Watch out for first year generic prices: cute trick. For the first year a single company is given a monopoly and only required to reduce the price by 20%.  "See, the generic is almost as cheap as the brand," the rep will inform a doctor. This is a bad pro big-pharma rule passed by Congress decades ago I'm sure) by the way. Cheap is a relative term.

The pharmaceutical giant, Pizer has excuses, reasons why it withheld the data, for example, they  claimed the data is wrong because of biological plausibility: the molecule is too large to cross the blood brain barrier.

Really? I care if the molecule gets into the brain; maybe it's an advantage.  The brain has its own immune system which needs to be tweaked lightly. Ask anyone who has had a brain Herxheimer reaction knows. The Cytokine storm which may make you crazy results from peripheral cytokine reactions/overproduction primarily.  And there is no data the molecule cannot get into the brain. Cytokines get in the brain.

Alzheimer's is in part motivated by inflammation. Other major factors are: production of amyloid beta protein (AB) (plaques and tangles), genetic factors and multiple external factors.

It is thought that AB protein is a naturally occurring antibiotic which responds to inflammation. Discussed elsewhere. Lyme resides in the brain along with many  bacteria, viruses, protozoans. It is true that spirochetes have been reported to aid in the transportation of AB into the brain.  Infection (or colonization) may be omnipresent and therefore not the whole story -- or the most critical piece.

The vast majority of my patients present with cognitive complaints. Many or most Lyme patients, at one time or another fit the criteria for a disorder call MCI, minimal cognitive impairment. The mainstream medical community considers this a pre-Alzheimer's condition, often.

What's a Lyme patient to do?

First off, if symptoms completely resolve with usual therapy do nothing.

If you are a patient who has had very aggressive therapy, e.g. months of IV antibiotics and cognitive symptoms persist, look up MCI and consider the following:

Get an AB PET. The tests measures metabolic activity in the brain and the presence of early AB protein deposition. IF the test is positive you are at very high risk for developing Alzheimer's.

Prednisone and Enbrel have largely been dangerous seen as because patients are misdiagnosed and not also treated for Lyme. Enbrel is likely tolerably safe, in many cases, considering benefit to risk ratio.

A lot of money has been spent searching for an Alzheimer's cure. To no avail. Nothing very promising in the literature.

I for one am very angry with Pfizer. I suppose it is typical behavior in the industry. We still need big pharma. Don't throw out the baby with bathwater. Hold them accountable. But, do not  conclude big pharma is corrupt therefore all drugs developed through the system are fruit of a poisoned tree and are therefore inherently untrustworthy and dangerous -- in addition to being immorally overpriced.

It's a bad syllogism. Drug companies are a very necessary evil.

Getting back to Enbrel Is this a silver bullet?.  More comment, biostatistics and analysis are required as well as prospective RCT medical studies. Since the drug will be generic soon big pharma will not finance the research. Fortunately, Alzheimer's, a burgeoning epidemic as our population ages, is well funded through private sources.

Ideal prospective studies, which will likely be done make observations moving forward starting with a baseline current population. The process is slow.

Retrospective, population studies, primarily manipulation of data already there will not take long. These studies are never as good as prospective studies but perhaps good enough.

If you want my  bottom line: don't run out and get Enbrel-- YET.

I am not endorsing the use of the drug for any medical condition, including Alzheimer's,
This site is for informational purposes only.  Medical care can only be delivered by a certified medical practioner who properly evaluates your particular issues. Please don't diagnose or treat yourself. 





Monday, May 20, 2019

Posttreatment Lyme disease case


A 52-year-old female was seen in my office several months ago.  She has a history of tick bite and bull’s-eye rash treated with recommend "standard" doxycycline for 3 weeks and she felt well -- until she didn't.  Symptoms appeared gradually.  Eighteen months later18 months later she complained of: incapacitating fatigue, poor sleep, diffuse pain, weakness, numbness and tingling, headaches, cognitive impairments–trouble remembering words, impaired focus and attention and memory loss, to the point of disability. She was hanging onto her job by a thread.

She also experienced severe night sweats but had chalked it up to menopause. The  sweats however,  were new and drenching, occurred several days weekly and  were qualitatively different from previous night sweats -- primarily hot flashes. 

With further question she stated she had been experiencing gasping mid-sentence and thought  she had developed a tic. 

Lab testing was positive for Lyme (CDC, IgM and IgG) and Anaplasma.

Lyme was initially treated with a triple regimen, doxycycline, rifampin and Tindamax. Also covers Anaplasma. 

Within 4 months she reported getting her life back and regaining a high level of function. Babesia symptoms, well described above (night sweats, air hinger) persisted.

The treatment was changed.  Rifampin was discontinued.  Doxycycline, Zithromax and Mepron were prescribed. 

Notes:  Typical  posttreatment Lyme disease, relatively early presentation (in my practice). The role of coinfection has been ignored in clinical studies.  Lyme as sole infection, absent coinfection is rare. Coinfections may be difficult to diagnose because of poor diagnostic testing.
Human trials have used only doxycycline and Rocephin. In mice, triple IV therapy: daptomycin, doxycycline and Rocephin (ceftriaxone) was shown to eradicate Lyme spirochetes.  

Medical literature suggests that about 20% of early patients treated by CDC standards will have chronic symptoms.
Many reasons have been suggested, Including:

Tick inoculates human host with antibiotic resistant biofilms.
Coinfections.
Strain specific virulence factors.
Host specific immune responses. 
Host already infected but asymptomatic.

Standard therapy ineffective -- high failure rate unacceptable, leads to chronic illness and/or serious sequalae.

Clinical approaches may include: 

More aggressive cocktail therapy early
Careful monitoring of patient for persistent symptoms and symptoms suggesting coinfection and early treatment
Not telling patients: don't worry, symptoms will clear.

Tuesday, May 7, 2019

PANDAS/PANS and Lyme, clinical notes


PANDAS and Lyme.

Based on my beliefs and clinical experience.

Mainstream medicine currently does not recognize PANS, the notion that other infectious organisms can induce the same disorder or exacerbate the disorder.
PANDAS stands for: Pediatric autoimmune syndrome associated with streptococcal infection. 

PANS stand for Pediatric autoimmune neuropsychiatric syndrome.

I would suggest the proper acronym is ANS.  The disease is not limited to children and occurs in adults.  

Mainstream view: Strep only.  Autoimmune, not related to persistent infection.
Alternate view:  Multiple microbes may be involved including tickborne pathogens: Lyme and Bartonella. Maybe others. 

When confronted with something new it is only natural that doctors compare the disorder to other similar ones, well described and put place the new illness into a similar, pre-made boxe..  Streptococcus is well known to be associated with a variety of syndromes which may be averted with early treatment. The syndromes in question are autoimmune and post-infection – as  every medical student knows and include rheumatic fever and glomerulonephritis. 

Rheumatic fever (RF) can weaken heart valves, cause arthritis and lead to a movement disorder. RF is rarely seen these days. 

PANDAS was put in the box of RF. Lyme, not even considered, would likely be put in the same box if so discovered. 

Most practitioners see PANDAS, PANS as a subset of autoimmune encephalitis. Therefore, the RF analogy is incorrect.  PANDAS/PANS is something else.
Novel autoantibodies have been discovered, i.e. Moleculera Cunningham panel.
PANDAS/PANS (PP) responds to IVIG. IVIG  has not benefited acute RF in clinical trials. 

Immune modulation with drugs for autoimmune encephalitis including rituximab has helped some patients with PP (with other therapies). 

PP is associated with sudden neuropsychiatric symptoms which appear overnight.
Typical symptoms include:  change in behavior/personality, OCD, tics, Tourette’s, anxiety, ODD and others. 

The disorders are not limited to children. There exists a population of adults, long treated with psychiatric drugs, ineffectively, who have persistent PP symptoms which may respond to PP therapy to be described. 

Primary therapies include: IVIG and antibiotics. 

In patients with chronic Strep pharyngitis/tonsillitis tonsillectomy may be of benefit.
The duration of antibiotic therapy and of IVIG is best left open. Every patient is different. 

If Step is the only concern drugs like amoxicillin or Zithromax may be adequate.
IVIG. Two issues to discuss. 

One theory is that treatment need be given only once every 6 months the other is it must be given every 3-4 weeks.

Dose: Getting approved for IVIG is difficult. Getting IVIG approved for the optimal dose is more difficult. 

There are 2 general sets of illness and 2 dosing sets. 

Neurological disorders are treated with high dose IVIG (1.5- 2 gm/kg) and immune deficit disorders low dose IVIG (0.4-1 gm/ kg)

PP patients are usually only approved for low dose therapy. 

(I am not saying the patients who truly have an immune deficit will not benefit from low dose therapy, rather I am say PP patients will receive an inadequate dose). 

There is a theory that low dose IVIG can actually make PP worse. I think this may apply when the therapy is given subcutaneously once weekly, not IV. Patients should receive IV therapy. The starting dose is generally around 0.6 gm/kg and the dose may be titrated upward based on clinical effectiveness. Published data with other forms of autoimmune encephalitis suggest doses as low as 0.4 gm/kg have been helpful.

Patients with Lyme, more often than not, also are infected with Bartonella and Babesiosis. 

Therapy should start with doxycycline because it covers a wide array of other coinfections and possible contributors, such as Mycoplasma. 
Bartonella therapy is generally inclusive of Rifampin/rifamycins and possibly Dapsone. 

I think Dapsone may not be a great Lyme drug but rather have great activity against Bartonella. 

As discussed elsewhere, antimicrobial choices may need to be shifted to cover the complete array of coinfections, including Babesia. 

Antimicrobial therapy, in the presence of tickborne pathogens may need to be low and slow because of the risk psychiatric Herxheimer reactions and worsening of autoimmune neuropsychiatric symptoms.

If Step is primary a higher dose needs to be used. Something like Keflex might be a consideration since it kills only Strep and no tickborne pathogen that I am aware of. This is the idea that targeted therapy may reduce psychiatric Herxheimer effects.

I reiterate: I think medicine is a weak science.  In PubMed there are hundreds of thousands of references to hypertension and yet recommended therapies seem to change every year or two. 

Medical studies, by necessity are internally valid. Yes, there are biases from the get-go. Aside from that: inclusion criteria are narrow (symptoms and lab tests), therapies are limited, e.g. one antibiotic and endpoints are narrow – e.g. one symptom is evaluated, such as improvement in cognition. To date, study groups have not used consensus methods (each group have evaluated the symptom with a different set of tools).
Studies frequently lack external validity or real-world application.  Minimal results are expanded, generalized -- to fill an ethos of preexistent belief about the inherent nature of the disease and its appropriate treatment. 

Evidence Based Medicine as a construct only looks at clinical studies, frequently deficient, and excludes basic science research and “biological plausibility.”
PP remains “controversial” and contested much as does Lyme writ large. What else would you expect?


Not to be used to diagnosed or treat any patient or particular illness. My clinical impression are presented strictly for general informational purposes.




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.