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Saturday, November 26, 2011

Lyme labs and babs

A 22 year old female had a tick bite with at rash at age 5 (recalled by mother). Her pediatrician treated her for 3 weeks. No symptoms recalled. At age 10 she had another bite, treated the same way, no problems. At age 12 she found herself not feeling quite right. It started with vague aches and pains, loss of energy. Her pediatrician diagnosed growing pains. She still did not feel well. Her concentration at school lessened, straight As were replaced with Bs. Her pediatrician diagnosed pre-teen hormones and prescribed reassurance. An avid athlete and enthusiastic basketball player, she collapsed on the court at age 13. The cardiologist and neurologist gave her a clean bill of health.

Her state of well being fluctuated. She had good and bad days, good and bad months. High school was a struggle. She had little time for friends or extracurricular activities. She started going to sleep at 7:30 and having a hard time waking up. She maintained her grades, B+: memory, concentration and focus were poor.

At 16 her pediatrician referred her to a psychiatrist. A diagnosed of depression made she was started on Zoloft. Maybe it helped; maybe not.

She finished one year of college but had to drop out. She had more memory problems, fatigue, joint pains, headaches and other symptoms.

Her mother asked her doctor to do a Lyme test. The test showed a negative ELISA and a positive Western Blot with a 41 IgG band and 41 and 23 IgM bands. The ah ha moment. She was treated with doxy for a month. Didn't help. The infectious disease specialist had nothing to offer. A friend referred her to me.

A repeat Lyme Western Blot 6 months later showed now only a 41 IgG band. The co-infection panel was negative.(I later noted that the B duncani test had not been done).

Her symptoms were typical in my experience for chronic Lyme: fatigue, brain fog, cognitive problems, numbness and tingling in the extremities, headaches, neck pain, muscle pains, migratory joint pain of both large and small joints and prominent depression.

She was treated with an aggressive anti-Lyme regimen. She felt worse over the next two months. Two months later a new symptoms emerged: profound night sweats, air hunger, flu-like symptoms with low grade fevers. A repeat round of lab tests showed a positive titer to B. duncani at the lowest cut-off point. Anti-babesia therapy was started. She had prominent nausea and Mepron intolerance. Zofran was needed to manage the nausea. Over time she began to feel better.

A new Lyme Western Blot from a different laboratory showed 58 and 41 IgG bands and a 41 IgM band. There was a partial reaction at the 23 band.

She continued to improve over the next six months. However cognitive problems were slow to respond. Intravenous treatment was discussed. There was an insurance snag. PICC never placed. Two months later she seemed to be better nonetheless.

A year into treatment she is doing pretty well. After a year at home she is back in college doing fairly well. Symptoms, especially night sweats quickly relapse off Malarone. Still a problem.

Follow up LabCorp testing, including B. ducani was negative. We were specifically looking for a positive Lyme test for insurance, not clinical reasons.

An additional Lyme Western Blot was sent to Stony Brook. This test showed: 41 and 60IgG bands and 18,35,41,72 and 93 IgM bands. I thought this was a definite positive.

Clinical note: The odd Babesia scenario has been relatively common in my practice. Initially the patient denies any symptoms suggestive of Babesia. Babesia symptoms only become prominent after Lyme therapy has been started, as if the Lyme Herx somehow awakens the sleeping dog of asymptomatic chronic babesiosis. The two players seem to act together.

Lab comments:

My confidence in Western Blots is waning. Different laboratories frequently come up with divergent results - not even close.

I am sure this patient has a form of babesiosis. Still, one laboratory I use frequently turns up positive results for B dunani at the lowest cut off point, frequently in patients who would otherwise show a negative Lyme/co-infection panel.

Could the reported "WA1" IgG antibody actually cross react with a different organism. Or, are there a lot of false positives? Dr. Fry suggested this may be a cross-reaction to a non-Babesia protozoan which he has identified.

In truth, sometimes I order a lot of Lyme related tests searching for the positive that might justify IV therapy if anyone is looking.

Another lab's Western Blots would have undoubtedly showed different results. Maybe its best to look at Lyme Western Blots from several labs if it doesn't break the bank.

History

History instructs us, oft the best predictor of the future.

Infectious plagues, epidemics and endemic, have molded the course of human history. The Black plaque, or black death - Bubonic/pneumonic plague of the 14th century has been called the greatest European catastrophe in history. Houses were emptied, villages abandoned, fields were littered with dead. The mysterious disease syphilis followed soon after, infecting many prominent world leaders, forever altering the course of human history. Henry V111, Francis 1 of France, Pope Alexander Borgia, Ivan the Terrible, and many more. Napoleon's madness was perhaps molded by Typhus. Epidemics of malaria, yellow fever, tuberculosis, influenza and AIDS were yet to come. The Spanish flu of 1918-1919 killed more people than WW1. Woodrow Wilson, the American president, contracted the flu while in Paris working out the details of the Treaty of Versailles. One could ponder: would things have worked out differently if he had been well?

Syphilis is perhaps the most pertinent to our story. A painless frequently unseen chancre is followed by a benign secondary stage a long latent stage and then a tertiary disease with protean manifestations. This "great imitator" can attack almost any organ in the body, frequently with central nervous system involvement. End stage disease,"general paresis," manifests itself with various symptoms: headache, "lightening pains," impotence, epilepsy, joint pains, progressive personality and cognitive changes, frank dementia and many more. Some infected have no symptoms and still transmit the disease to the unborn.

Every point in history, has to some extent, been intertwined with and perhaps influenced by its own epidemic(s).

Perhaps epidemics can be less obvious and still alter the history of mankind: no putrid cough and waisting of consumption/tuberculosis.

Perhaps there can exist a silent epidemic: an insidious creeping crawling yet quiet plague.

I know someone. An acquaintance let's say. A fifty something, suffering with fatigue, depression, joint pains and cognitive problems. He believes his family doctor and believes in the "system." The Lyme test was negative. Not Lyme. "Please see 'Under Our Skin.'" Not interested. The person, as of this writing continues to see a panoply of specialists and even non-traditional herbalists. Not Lyme.

I cannot raise the topic of Lyme, now a touchy subject. "You think everything is Lyme."

Arthritis. Fibromyalgia. Chronic fatigue. MS. Early dementia. POTS. "not feeling as well as 80 year old parents." All on the rise - and others.

A quiet epidemic. Denial. "Aches and pains of daily living." "Anti-science. Unseen.

True story: Tall sailing ships, those of Christopher Columbus were sailing to the Island of Hispanola. The natives scanning the horizon could see nothing. Perhaps a perturbation of the waters. After all, such things could not exist in their universe. They called the Shaman. He saw the ships. Only then could the people see them too. (to their detriment, but that's another story)

The 19th century European obstetrician. Semmelweise literally lost his mind trying to convince the experts that puerperal fever (child bed fever). a lethal epidemic, was caused by germs and that hand washing was the cure. He gave up everything to fight the battle against prevailing world opinion. Not living to see the paradigm change - slowly, he died pitifully in a mental hospital.

What can we see in the calm - no turbulent waters?

Thursday, November 10, 2011

Iceman

Readers know - the suffering of Lyme is so great that contemplation of suicide is common. And then to make matters worse - so often, the degree of misery is unseen by those closest.

Many suffering with Lyme have heard from others: "I had Lyme: it was no big deal."

"He should only be in my body for one day!"

Maybe these unsympathetic individuals actually had a different version of the disease.

It turns out "Lyme" may a wide diversity of clinical presentations because patients are frequently infected with different strains of the organism.

Maybe we can begin to answer the question: why do some patients infected with Lyme with the tell tale EM rash never become sick without treatment, while others infected with Lyme disease treated early with recommended doses of antibiotics go on to develop full-blown chronic Lyme disease?

Research has shown that some strains of Borrelia burgdorgeri are more virulent, quickly causing dissemination into tissues, while others strains are relatively benign and may be associated with little or no disease. Borrelia bacteria show a surprising amount of genetic diversity.

Lyme bacteria have been here for thousands of years providing a long time frame for evolution and differentiation. The famous iceman dug up from the permafrost in the Italian alps in 1991 has now had an autopsy. The DNA from a fragment of hip bone showed an unexpected finding: Borrelia burgdorferi. Likely, persisting DNA from cystic forms. Still, I am surprised not only that Bb was found, but that it was found in bone.

The Lyme epidemic is world wide and has been found in all the continents with the possible exception of Australia.

It is confusing that bacteria with names like: B. afzeli, B. bissette, B. miyamotoi all cause "Lyme disease."

The international organization with classifies bacteria calls all species of Borrelia which cause human Lyme-like disease, (12 or more species) "Borrelia burdorgferi sensu latu." These associated illnesses have varying degrees of similarity and dissimilarity to our Lyme disease. Some of these species have crossed borders into other regions.

The Lyme disease bacteria we usually think of(in the US)is called Borrelia burdorferi sensu strictu. Even within this narrower sub-species of the Lyme community the genetic diversity is mind boggling and mostly unknown.

A recent scientific publication from the American Journal of Pathology studied three sub-strains of a sub-strain of Bb sensu stricto and found one sub-sub type to be more pathogenic than the others two.

To illustrate how diverse the Lyme zoo is: The study examined the pathogenicity of three strains of Borrelia burdorferi sensu strictu, Osp C (type A) known as RTST 1,2 and 3.

The Lyme Osp C (outer surface protein) is associated with the 23 band on a Western Blot. Its molecular weight can actually vary from 20-25 Kds. The OsP C protein is quite variable. Twenty-one types have been identified. One of these Osp C types, type A, was subdivided in this study into three more sub-variations based on " ribosomic RNA intragenic spacers." One was nastier than the others.

In other words, there are a gabillion versions of Lyme, some making us sicker than others.

Treatment may be difficult because of this unknown variety of strains. It is well documented that a single host can be simultaneously infected with multiple strains.

Of note: Dr. Allen Steere is one of the authors of the above described study.

Sunday, November 6, 2011

Lyme: the tissue pathogen

It has long perplexed me why Borrelia bacteria appear to be so abundant in the blood of other mammals but so sparse in human blood. An Ixodes tick, generally the poppy seed size nymph form has a blood meal, typically from a mouse, becoming infected with Lyme along with an assorted host of other co-infecting germs. Even though the tick takes many such meals - (how much blood can the tick eat)? - it would appear that spirochetes must exist in fairly high numbers in circulating blood in these other mammalian hosts.

In humans the paradigm/narrative states: the spirochetes stick to the extracellular matrix, become intracellular, convert to cyst forms, avoid immune defenses and antibiotics by avoiding blood and body fluids and finds safe harbor within biofilm communities.

"It is a tissue bacteria, not one to be found in the blood."

Now thinking about these statements they do seem wrong. Textbooks have instructed me the bacteria is spread via the blood stream. I conveniently discarded this explanation along other textbook things Lyme. But - Lyme bacteria cannot spread to many disparate tissues including the central nervous system unless carried by circulating blood. Of course I knew this. Right.

We have looked for the bacteria in blood of infected humans by PCR testing, a direct assay for detection of Lyme DNA. This is what has mislead me. The results have been almost always negative. Getting a positive PCR for Lyme has been like hitting the jackpot.

With improved culture techniques Lyme bacteria have now successfully been cultured from human blood consistently.

Culture is the absolute gold standard for proving the presence of the bacteria and chronic Lyme disease (not post Lyme syndrome).

Why the negative PCRs?. PCR technology uses primer pieces of DNA which target sub-regions of the organism's complete genome. These reactions are amplified and read by a machine. The primers target specific regions of DNA known to be conserved within different strains of the organism.

Sample size may be an issue. The PCR machine may be sampling a small amount of DNA taken from a small sample of blood. PCR testing may not be sensitive enough to detect the most minute traces of DNA. There are also various technical glitches which may occur with the technology.

With culture techniques a larger amount of blood/DNA may be tested. Perhaps this is why culturing has been more successful.

Bottom line: new staining and culturing techniques may be shattering another part of the paradigm. Lyme is not just a tissue pathogen in humans but can usually be found in blood if you just know how to look for it.