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. 

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.

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.

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.

Antibiotics and Germs

Its still complicated but I am trying to explain some basic concepts for the lay person.

Antibiotics only kill germs called bacteria.  Germ is not a medical term but a colloquial substitute for pathogen, a microorganism of one sort or another that causes human illness.

Disease causing germs are representatives of various families in the animal kingdom of microbes, including:  bacteria, viruses, fungi, yeast, protozoans and worms .

With few exceptions, antibiotics kill only bacteria so that is what we will discuss.

Bacteria are one cells prokaryotic microbes, so named because they lack an organized nucleus.

Please keep in mind that the vast, vast majority of bacteria are friendly or harmless, including the 2-6 pounds of normal “flora” we carry around, necessary for immune functions and detoxification.

Bacteria present as a menagerie of forms and shapes: comma, spiral (spirochete), cocci (round), rod (elongated), chains, grape-like groupings, filamentous etc.

THE SHAPE OF A  BACTERIA DOES NOT DETERMINE WHETHER IT IS A PATHOGEN, A GERM.  ONE SPIROCHETE MAY BE NORMAL FLORA, HARMLESS, AND ANOTHER MAY BE LYME.

Families of antibiotics may contain similar members. Members of the same family may perform different.

In general, specific antibiotics target bacterial germs which possess certain characteristics.

For example, an antibiotic may target bacteria with cell walls constructed  somewhat differently --  gram negative or gram positive. Antibiotics may target gram positive bacteria, gram negative or others such as intracellular bacteria etc.

Intracellular bacteria may only survive in host cells: some have no cell wall e.g. mycoplasma.

Bacteria (think Lyme) may lack a cell wall but rather have a double outer membrane.

Antibiotic classes include penicillins and cephalosporins which are considered cousins because both share a  ring structure (beta lactam). The drugs are divided into generations. First generation, second and third.

With progressive generation more types of bacteria are killed (broad spectrum versus narrow spectrum.  


Antibiotic classes include tetracycline, macrolide, sulfa, rifamycin, quinolone, antiparasitic, e.g. (Flagyl (nitroimidazole) etc.

We use principals of pharmacology to decide which antibiotic(s) to use for a particular infection.  Deciding factors may include the severity and location of the infection.

We consider MIC, minimal inhibitory concentration and MBC, minimal bactericidal concentration.  This means the amount of antibiotic to inhibit growth or to kill the bacteria.

We must consider the risk of side effects and complications, like C. diff colitis.

We have to make sure the antibiotic can get to the source of trouble, for example the brain, with ability to transverse the special BBB) blood brain barrier.

There are a lot of very complex factors that influence antibiotic decision making.

Treating chronic Lyme disease is a vary complex process.  As  with a patient I saw this afternoon, Lyme  triggered a cascade of problems, including: dysautonomia (POTS), MCAS, mast cell activation syndrome. 

She also suffers with a very stubborn case of babesiosis.


There are a lot of balls in the air to juggle.

 A recent live Facebook event was successful.
I hope we will soon cut through some of the confusion.

I will be scheduling another live Facebook presentation: Treating Lyme with Q&A in the near future. My Facebook coordinator Brittany Goff will be setting this up.

Lyme, evidenced based medicine, Fallon and the Institute of Medicine

I recently gave a talk about Lyme and EMB, evidenced medicine.  I had no idea that Brittany, who runs my Facebook page, live-streamed and posted the talk on Facebook.

The Institute of Medicine holds a lot of sway in the medical community.  Something called “patient centered medicine” is said to be enshrined.  There are many facets to patient centered care -- the one of interest to me here is that patient preferences are given credence.  In fact, the IOM states not to consider patient preferences is morally wrong, a violation of patient rights.  Vocal critics say this ignores EBM, evidence-based medicine. Not true. EBM is part of the consideration, not the only consideration.

Evidenced based medicine doesn’t require consideration of scientific plausibility.  If the results of a study contradict accepted science or reality, then it is likely the study if flawed. 

This is about where we are with Lyme disease, I think.

All clinical trials are flawed and biased in many ways. The interpretation of results is frequently fraught. Text books of statistics  are full of complex mathematical equations and show innumerable ways of crunching the same data and numbers.   If an investigator does not like the conclusions, other statistical models can be tried until he finds the one meets the objective: support preexistent beliefs.  It is like trying on new shoes. This is particularly true when subjective questionnaires are used for endpoint analysis.

To avoid bias: Methods of statistical analysis is a variable which must be controlled, delineated before the start of the trial and strictly adhered to.  Appropriate clinical questions need be determined  at the outset. 

For medical studies THE statistical question is: did the treatment benefit the treated cohort in a manner that cannot be explained by chance alone?  Or with 95% certainty.

In the Fallon study:  Did treated patients have cognitive improvements 12 weeks after therapy compared to the group given placebo, by statistical analysis?  In the treatment group were improvements in fatigue durable after 24 weeks? The answer in each case is yes.  As Dr. Fallon later states, the study shows efficacy: the treatment works.

Those who claim the study was negative are looking at the wrong question.

The study showed:  IV Rocephin 10 weeks caused cognitive improvements at 12 weeks which later, without further treatment reversed, whereas--improvements of physical symptoms like pain, fatigue and function were maintained at 24 weeks.  

The study conclusion stated the treatment was not effective for PTLDS.

This never sat right with me.  The conclusion is not reflective of what the study shows.  Do University internal politics had something to do with crafting the wording. This process is certainly not transparent.

The terms efficacy and effectiveness sound the same but are different.  Efficacy is the demonstration of A positive clinical response to treatment.   Effectiveness refers to successful clinical use of a treatment as a whole.

The second standard had the same chance of being proved as threading a camel through the eye of a needle.  The first standard shows proof of concept and that is huge. The conclusion does not reflect the paradigm shattering enormity of the study.

The favored null hypothesis of mainstream medicine in 2007 (and now?) was:  Persistent symptoms after Lyme treatment is a post treatment Lyme syndrome, an autoimmune affect, all the (clinically significant) spirochetes (Borrelia burgdorferi) have been eliminated.  

Fallon’s study proves the alternative hypothesis: Post treatment symptoms are associated with persistent infection and respond to additional antibiotics.

The IDSA makes the classic type I mistake of failing to discard the incorrect null hypothesis.

EBM -- IDSA guidelines were written on the basis of a glaring mistake of logic and statistics.

Biological plausibility, although not a necessary consideration here, was not looked at.  The fact that Lyme had not been eradicated in animal models then (and now) suggested that persistence of Lyme in human cases is highly likely.  The results should not have been surprising. 

In the IOM approach, EBM is decided by a closed panel, opinion driven, and at best provides narrow endpoints lacking generalization. The two other key elements of patient oriented medicine are medical judgement and experience – the art of medicine and patient preferences.

The IOM argues that clinical experience is necessary to fill in gaps or gaping holes left with only the EBM approach.  The IOM brilliantly exposes the inherent weakness of EBM.  Within this framework doctors are healers in the traditional sense and allowed to figure out the puzzle each patient is. This is critical when the disease is extremely complex and multisystem.  

My next talk will be about treating Lyme.  I want to get into some specifics.  I hope to tease out the roles of science, EBM, clinical experience, patient preferences, and the principal of first do no harm.

.

Lyme and the plague

A perfect storm.  It was a perfect storm which led to the spread of the bubonic plague endemic which hit Europe in waves over more than 5 centuries.  The plague is a vector borne zoonotic disease and, in this way, similar to Lyme disease. The reservoir for the disease is rats who travelled in the bowels of trading ships making new homes in heavily populated port cities and other population centers. The vector was not a tick but rather an unsuspected rat flea which carried the deadly bacteria, Y. pestis.  The infection led to gruesome deaths killing half the population of Europe and decimating much of Asia, killing a third of the global population. Plague doctors suspected the disease was carried by a miasma, bad air, perhaps carried by birds. They donned scary beaked costumes and bled patients to rectify an imbalance of the 4 bodily humours. Some of their patients lived; the mortality rate was somewhere between 40-90%. When patients recovered, they claimed success. It was a perfect storm because populations became increasingly concentrated in cities like London, trade was active amongst Europe and Asia and the rat hitchhikers found wonderful new homes with food and shelter and because at the height of the plague, around 1360, the germ theory of disease would not be discovered for another 500 years. 

Today, Lyme, and some consider a silent plague has much in common with the black death.  Lyme disables rather kill and the subtle manifestations, or not so subtle if you look carefully, go unseen by the Medical community, writ large.  In this case birds really do transmit the disease increasing tick habitat over years and decades.  Rather than staying close in cities where one can walk everywhere, the car led to populations spreading out, suburbs abutting wooded areas and habitat for animals including Lyme requisite mice and deer.  Deer became increasingly plentiful. Predators, like mountain lions were scarce.   Mice thrive because potential predators: fox, raptors, owls and others moved away as well.  Deer, mice and ticks increased dramatically in number.  Over time, tickborne pathogens flourished and more and more ticks became infected, now most ticks (deer ticks and lone star ticks), with Lyme and other nasties. 

Betty was reading a book, enjoying a glorious late spring day, lounging in her chair next to the garden she planted in her back yard, a yard shared with so many beautiful white tail deer. Her husband Bob, sweating in the sun, smiled at her, enjoying the task of clearing brush in the wild back of the property. 

Betty developed fatigue, malaise, diffuse muscle pains, night sweats, brain fog, depression and irritability.  She visited her GP who even did a Lyme test (just to be thorough) and diagnosed depression, sending her off with a bottle of Prozac. 

Bob developed strange rashes, headaches and numbness and tingling in his feet.  His doctor suspected neuropathy and this was confirmed by an EMG.  His blood sugar has been borderline and his father has diabetes. He was sent home with a diagnosis of diabetic neuropathy and a bottle of Neurontin, gabapentin. 

The idea was developed by Pasteur in the 1850s and further worked out by Koch in the 1860s-1870s. The germ theory was born. Poor Semmelweis, an Austrian obstetrician in the 1840s went mad asking only that colleagues wash their hands, to prevent so many childbed fevers and deaths of newborns and their mothers, but no one listened. 

Penicillin, the wonder drug of the 20^th century was discovered in 1929 and mass produced in the middle of the second world war. 

Medical knowledge and science have exploded exponentially. The entire human genome has been sequenced.  HIV/AIDS has been conquered.  People no longer die from small pox, syphilis, tuberculosis or the plague.

So why I ask, do the modern-day doctors caring for these two souls afflicted with disabling if not deadly illness, treat them with the same level of knowledge, expertise and self-confidence as bird costumed plague doctors of 1360 bleeding patients to correct bodily humours?  Of course, we know.  But nothing can justify the horrific sentence of misery imposed on these unknowing and trusting patients.  Before long, Betty will have lost her mind, become confused and suicidal and admitted to a psychiatric hospital for electroconvulsive shock therapy.  Bob will have become progressively weaker confined to a wheelchair with the diagnosis of autoimmune CIDP, crying every night, trying to comprehend what has happened to his beautiful, wonderful wife.  

It feels like Semmelweis all over again. 

Note: case presentations fictional.