Archive for October, 2017

Is Chronic Lyme Disease – Not Lyme Disease At All?

Is Chronic Lyme Disease (CLD) actually Lyme disease? That’s one of the questions asked during the Simmaron Research Foundation’s Patient Day in September.

It was a full room in beautiful Incline Village sitting on the northern shore of Lake Tahoe in Nevada. Emily Taylor of SMCI came up from LA, Gunnar took time off from medical school. Maureen Hanson and Mady Hornig flew over from the East Coast; Dr. Konstance Knox from the Midwest. The locals included Anita Patton, Courtney Miller, Eric Johnson, and, of course, there was Dr. Peterson.

chronic lyme disease

Why some people remain ill after being treated for Lyme disease is a vexing question

Why some people who have been treated for Lyme disease remain ill is a knotty question, and it has pertinence for chronic fatigue syndrome (ME/CFS). Both in Lyme disease and chronic fatigue syndrome (ME/CFS) many people become and then remain ill after an infection.  Why that happens is a mystery.

Some people think that chronic Lyme disease is simply another subset of chronic fatigue syndrome; that the Borrelia burgdorfii infection which ticked off chronic Lyme disease is no different from the herpesvirus or enteroviral or  other infection that just happened to send ME/CFS patients’ systems into a tailspin. The idea is that it’s not the infection, it’s the fact that an infection occurred.  That’s what the Dubbo and other studies which have shown that ME/CFS can be triggered by a large of number of pathogens suggest.

Others believe that the Borrelia infection is still there, deeply hidden, but grinding away in the chronically ill.

No one knows, but the idea that different pathogens are causing similar issues in ME/CFS and Lyme is belied by a study which found significantly different proteins in the cerebral spinal fluid of ME/CFS and Lyme disease.

Dr. Konstance Knox believes the two diseases may, in fact, be very different. In her Simmaron Patient Day presentation, she suggests a pathogen may be present in chronically ill Lyme disease patients but not the Borrelia bacteria; she believes that a tick-borne virus called the Powassan Deer Tick virus, which at its worst is fully as dangerous as Borrelia or more, may be doing its work.

 The Powassan Deer Tick Virus

The Powassan Tick-borne virus was first isolated from a person from Powassan, Canada in 1958.  (Powassan, like Lyme, Connecticut, is another small town that just happened to get stuck with the name of a disease.) The Powassan virus is a Flavivirus related to such nasties as Zika, Dengue, West Nile Virus, and tick-borne encephalitis virus (TBEV). All these viruses can cause brain swelling (encephalitis).

The scariest thing about the  Powassan virus is how quickly it can be transmitted. Because the Borrelia bacteria that causes Lyme is carried in the stomach of a tick, the tick has to feed for quite a while before the bacteria actually makes into humans. Because the Powassan virus, on the other hand, is carried in the saliva of the deer tick, it takes a mere 15 minutes or so for it to jump from a feeding tick into your bloodstream. A Powassan infected tick can jump on, feed for a bit – transmit the virus – and then jump off, without you ever knowing it.  Since ticks are so small and POWV transmission so rapid, few patients with Powassan encephalitis recall their tick bites.

Powassan virus symptoms - CDC

Most cases of Powassan virus infection are mild but at its worst a Powassan virus infection rivals Lyme disease in its severity

Most people infected with Powassan Virus (POWV) experience flu-like symptoms such as headache, sore throat, drowsiness and disorientation.  If the infection spreads to the brain, the virus can cause everything from lethargy, high fevers, vomiting, respiratory problems and difficulty speaking to paralysis, seizures, coma and even death.

Powassan-triggered encephalitis is accompanied by the infiltration of lymphocytes and monocytes into the brain and the widespread destruction of neurons in the motor areas of the brainstem (affecting movement), the cerebellum, basal ganglia (potentially affecting movement again) and the thalamus. MRI’s pick up only non-specific abnormalities and thus are not diagnostic but suggest that brainstem may be particularly effected.

Studies on Powassan infections are rare but some suggest that no less than fifty percent of Powassan survivors may be left with permanent neurological problems including partial paralysis, headaches, memory impairment and/or paralysis of the eye muscles.

A 2015 paper presenting eight verified cases of neuroinvasive Powassan virus infection in New England bore this out. Two of the patients died, four fairly quickly recovered and two exhibited from medium to long-term problems.  One 21 year old man who entered the hospital with vomiting, fever and confusion was given methylprednisolone and IVIG. He improved over time and left the hospital alert, oriented, and “speaking in short sentences”. He was unable to return to work for seven months.  Fifteen months later, a 52 year old man still had persistent headaches as well as problems with motor functioning and coordination.

Because surveillance of the Powassan virus has been poor, it’s difficult to estimate its true incidence in humans.  Luckily, far more ticks carry the Borrelia bacteria (20-50% of ticks in endemic areas) than carry the Powassan virus (1-10%). Unluckily, the Powassan virus appears to be spreading.

After Powassan virus caused the sudden death of a Massachusetts woman, a tick surveillance program found from 0-16% of ticks in a given area carried the virus. A Canadian survey suggested that 3% of residents of Ontario province in Canada had been exposed to the virus. These surveys suggest far more people have been exposed to the virus than suspected. Most undoubtedly experienced symptoms similar to those of a mild cold.  Others who were more seriously affected probably never got tested for Powassan.

Much of what we know about the Powassan virus comes from study of a closely related virus in the Europe and Asia called Tick-borne encephalitis virus which causes thousands of neurological illnesses every year.  Studies on the Powassan were almost non-existent until around 2011 when the research started picking up. Powassan virus is considered a “rare but severe neuroinvasive disease“.

Could Chronic Lyme Disease Caused by the Powassan Virus?

Dr. Konstance Knox,       Coppe Lab

Simmaron Scientific Board member and collaborator, Konnie Knox has been leading a recent surge in research publications on the Powassan virus. Her recent survey of the Ixoides scapularis ticks known to carry Lyme disease and Powassan virus in Wisconsin found that 5% carried the Powassan virus. Rather ominously half of the ticks carrying Lyme disease also carried the Powassan virus.

With Lyme disease fairly common in Wisconsin (@ 187 cases/100,000)  Knox’s finding strongly suggested that Powassan infections were being under-reported in Wisconsin.  (If Knox’s findings are validated, then Powassan virus infections probably occur on the order of at 90 cases per 100,000 in Wisconsin, or as much as 5400 cases per year.)

Next, Knox tested 95 patients seen at a clinic for possible Lyme disease over four months in 2015 in northern Wisconsin.  Lyme disease,  POWV, West Nile virus (WNV), Tick-borne encephalitis virus, V, yellow fever virus, dengue viruses 1–4, and Japanese encephalitis virus were tested for.

Powassan virus Lyme disease

Could chronic Lyme disease actually be a Powassan virus infection?

Serologic evidence of POWV infection was present in 10% of the patients and confirmed in 3% of them by other testing.  Almost half of the patients with an acute Borrelia infection were infected with the Powassan virus. When the patients with a validated Powassan infection were tested, 87% were also found to be infected with Lyme disease. None, fortunately, had signs of a neuroinvasive disease.

The fact that 10% of Lyme patients come down with Chronic Lyme Disease and, Knox’s findings suggest that about 10% of patients with Lyme disease may also be infected with the Powassan Virus, is of course, more than intriguing.

Could chronic Lyme disease or ME/CFS patients be suffering from a unusual, untreated infection? Knox’s present research into ME/CFS patients could help answer that question. Knox will be testing several hundred ME/CFS patients for evidence of Lyme Disease, Powassan virus, and other tick and insect-borne diseases.

Lyme Disease Or ?

  • Konstance Knox who owns a diagnostic laboratory, noted that Lyme testing has improved and that good Lyme testing is not impossible. (She liked the CDC protocol which calls for a two-step testing process.)  She’s confident in the results from her lab which uses machine testing rather than subjective human testing to assess the test results.

She noted that one of the biggest problems with Lyme diagnosis is getting tested too early. Because it takes about four weeks for the Lyme immune factors to show up in the blood, the tests aren’t accurate until you’ve been infected for about a month.

The Lyme diagnosis question, of course, is a big one.  Get it wrong, as the story of one ME/CFS patient in the audience indicated, and you could be in for years of expensive treatments which leave you worse off.  After a diagnosis based on neurological and non-specific symptoms, a CD 57 test, and a negative Western blot test from Igenex, this patient had been on and off antibiotics for about five years. Talking to her later she said she’d improved tremendously on antibiotics at times, but the treatment ultimately failed and left her worse off than ever. (She suspected that the anti-inflammatory effects of the antibiotics had temporarily helped.)

She would be in the chronic Lyme disease category except for the fact that she never have had Lyme disease in the first place. In fact, her symptoms didn’t really fit. She’d marveled at other “Lyme patients” who were able to exercise. Despite the fact that she’d visited a clinic that treated complex, chronic diseases, she didn’t know that her main symptom – post-exertional malaise – was the defining characteristic of ME/CFS until she visited an ME/CFS clinic last year.

Knox suggested that a lot of putative “Lyme” patients may not be Lyme patients at all. She’s found, for instance, a very low incidence of Lyme disease in Dr. Peterson’s patients, many of whom probably hail from the Western United States. She did, however, find evidence of a tick borne virus in about 11% of a 200 patient sample.


People who still suffer from the symptoms of Lyme disease after being appropriately treated for it are a medical mystery.  Some doctors believe the Lyme bacteria is still present. Others believe that the Lyme infection may have triggered an ME/CFS-like condition. Simmaron Research Foundation Board member and collaborator, Dr. Konstance Knox, believes some people with chronic Lyme disease may be suffering from an unidentified Powassan virus infection transmitted by the same tick.

Powassan virus is a poorly studied virus that can be quickly transmitted by ticks. While most people probably pass off the virus quickly, a neuroinvasive infection can cause serious symptoms including paralysis, stroke, coma and even death.

Dr. Konstance Knox’s studies suggest that Powassan virus is often present in ticks harboring the Borrelia bacteria that causes Lyme disease, and that about 10% of Lyme disease patients have been exposed to the virus. That’s an intriguing finding given that about 10% of Lyme patients come down with chronic Lyme disease.

Dr. Knox is currently studying the incidence of the Lyme disease bacteria, Powassan virus and other insect vectors in Dr. Peterson’s chronic fatigue syndrome (ME/CFS) patients. Stay tuned…


Ian Lipkin & Simmaron to Collaborate in New NIH ME/CFS Research Center

“These important grants will provide a strong foundation for expanding research in ME/CFS, and lead to knowledge about the causes and ways to treat people affected by this mysterious, heartbreaking, and debilitating disease,”

Dr. Francis S. Collins, Director of the NIH

Simmaron to Collaborate in Columbia’s Landmark NIH Center of Excellence

Dr. Lipkin (center), Dr. Nath (NIH Intramural study director), Dr. Unger (CDC ME/CFS director), Dr. Peterson, Dr. Hornig and others.

Dr. Ian Lipkin and the Center for Infection and Immunity at Columbia University have been awarded one of three NIH grants to produce a collaborative research center dedicated to ME/CFS. Simmaron’s Scientific Advisor Dr. Daniel Peterson is a clinical collaborator on the team.

This collaboration is the culmination of a 6-year partnership between Columbia, Dr. Peterson and Simmaron Research, among others, that have produced 6 peer-reviewed publications that have identified immune changes leading to new profiles of patient subsets.

The total research grant package – $35 million for three research centers and a data center over a 5-year period – is likely the largest single infusion of NIH funding into ME/CFS research ever. The highly competitive NIH process involved 10 grant applications from across the U.S.

In addition to Columbia, the three research centers – the first dedicated NIH funded research Centers in over 15 years  – include a Cornell Team lead by Dr. Maureen Hanson which will focus on the effects of exercise on the brain, the immune system and inflammation.  Another study lead by Derya Unutmaz of the Jackson Labs will determine how the immune system, the microbiome and the metabolism interact to cause ME/CFS.

Ian Lipkin – Pathogen Hunter

Nobody is better at pathogen research than Ian Lipkin, and no subject is more important than how a seemingly innocuous infection turned into a chronic, often debilitating and life-long illness for many.

If anyone is well-situated to explore that question, it’s Dr. Lipkin. A key innovator in the pathogen field, Dr. Lipkin was the first to show that genetic testing could discover new pathogens to science. Dr. Lipkin invented MassTag PCR, the first panmicrobial microarray, and was the first to use deep sequencing in pathogen discovery.

In 2014 Lipkin’s lab received a $31 million, five year NIH grant to establish The Center for Research in Diagnostics and Discovery (CRDD). Although the CRDD is not specific to any disease, one of its key goals is a subject dear to many ME/CFS patients’ hearts: understanding why infectious agents create enormous problems in some people but not in others. For example, identifying the “host factors” which turn a usually recoverable infection in a person with ME/CFS into a “never-ending flu” will be critical in learning how to turn the clock back in ME/CFS.

More recently Dr. Lipkin’s new method of viral analysis  was described as a breakthrough for precision medicine. Acclaimed as one of ten world-changing ideas of 2015 by the Scientific American, the new VirCapSeq-VERT test is able characterize the genetic composition of any virus in any bodily fluid quickly and cheaply “with exquisite sensitivity and accuracy”. Given the heterogeneity probably present in ME/CFS, Dr. Lipkin’s focus on developing tools for precision medicine – which focuses on identifying unique factors in each individual – is probably going to be helpful indeed.

In short, Dr. Lipkin’s extensive research record, his interest in the effects pathogens have on the body, and his ability to keep himself and his lab on the cutting-edge of science made him an obvious choice to host an ME/CFS research center.

Center for Solutions for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (CfS for ME/CFS)

“We will leverage every technological platform possible to solve ME/CFS. We will get there.” Ian Lipkin

Lipkin’s goal is a simple one – to come up with treatments as soon as possible. During a telephone conversation, Lipkin abjured the idea of an “ME/CFS research center”; he’s not building a center to research ME/CFS, he said, he’s building a center to find solutions for ME/CFS – hence the name “Center for Solutions for Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (CfS for ME/CFS)”. He anticipated that a variety of treatments are going to be needed for different people.

The new Center has three main aims – understanding how pathogens affect immune functioning and cause disease in ME/CFS, understanding links to the microbiome and host interactions, and developing a mobile app to better understand the symptoms and stressors in this disease.

Samples may be a problem for some but they’re not a stumbling block for Ian Lipkin. He and his colleagues have built a large biobank with the support of the NIH, the Chronic Fatigue Initiative and crowdfunded Microbe Discovery Project that includes feces, saliva and blood. What he hasn’t had is the funding to test them to the extent that he’s wanted to.

Now he has some of the money he needs carry out what amounts to his grand plan to study ME/CFS. Ultimately Lipkin hopes to figure out how an infectious trigger managed to wreak so much havoc on many people with ME/CFS.

Lipkin’s team will be using his VirCapSeq-VERT technology to get a snapshot of all the viruses a person has been exposed to. He’ll be using technology developed using a grant from the Bill and Melinda Gates Foundation to identify the bacteria present. He’ll also be assessing fungi.

Along with immune functioning he’ll be looking at autoantibodies, a hot topic right now. Fluge and Mella are pursuing autoantibodies in their Rituximab work, and autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS) – a condition many people with ME/CFS have. Just last year, a German study Fluge and Mella collaborated in, found autoantibodies to acetylcholine and beta-adrenergic receptors in about 30% of ME/CFS patients. The presence of these antibodies could help explain why Rituximab is helpful in some.

Noting the work Mark Davis of Stanford has done regarding T and B-cell responses, Lipkin said he hoped to work with him to use microarrays to try and determine what those cells are responding to in ME/CFS.

Daniel Peterson, M.D.

We haven’t thought of Lipkin as a metabolomics researcher, but he’s now engaged in no less than three metabolomics projects with Oliver Fiehn of the University of California Davis: a Simmaron Research Foundation cerebrospinal fluid project with Dan Peterson, a blood metabolomics study, and with the new research center, the first ever exercise metabolomics study.

Lipkin described metabolomics as a way to peer inside the body and see that chemicals that result from the body’s functioning. Reduced levels of neurotransmitters, for instance, could mean a balky nervous system, high levels of other factors could be suppressing the immune system, reduced levels of energy building blocks or by-products could reveal an energetic deficit affecting many functions.  Metabolomics will also help him determine if the metabolites from the bacteria in our bodies could be affecting immune and central nervous system functioning.

The team will also analyze the metabolites and gene expression before and after exercise tolerance tests and an  orthostatic intolerance test called the Lean Test, developed by NASA, which Dr. Bateman and the Bateman-Horne Center began piloting in an ME/CFS study. If metabolism is indeed a key problem in ME/CFS, we can expect the already striking metabolic findings in ME/CFS to get considerably more striking as exercise and standing tests put ME/CFS patients metabolism to the test.

Dana March and Tony Komaroff will also develop a mobile app called myME/CFS that will allow them to track symptoms in response to stressors and treatments. It will allow those with the disease to chart the course of their illness, and will allow clinicians and researchers to use these valuable data for insights. This will supplement work the team will be doing in mining existing databases for subtypes and risk factors.

Lipkin has more projects than he has money to fund them. During a Directors’ meeting at the NIH Lipkin pressed Dr. Koroshetz on the need for more funding for the research centers, but talking to him on the phone he said firmly, “We will get there.” He said his team would leverage every resource he can, and exploit every technological platform possible to solve ME/CFS.

Ian Lipkin, Dr. Peterson and the Simmaron Research Foundation

Dr. Lipkin’s interest in chronic fatigue syndrome (ME/CFS) – and his connection with Dr. Peterson – goes back decades. His first acquaintance with the disease, interestingly enough, came from one of Dr. Peterson’s patients way back in 1984.  Dr. Lipkin talked about that and his search for more resources in a 2014 video.

Since Dr. Lipkin re-emerged in the ME/CFS field through the XMRV studies, Dr. Lipkin and the Simmaron Research Foundation have collaborated on several ground-breaking studies. The Lipkin/Hornig blood cytokine study identified, for the first time, evidence of dramatic immune upregulation early in the disease followed by what appears to be an equally dramatic period of immune exhaustion.

A landmark cerebral spinal fluid study using Dr. Peterson’s samples found the same.

Next, Dr. Peterson’s years of experience informed another spinal fluid analysis which, for the first time, identified an “atypical” subset of ME/CFS patients who had dramatically different immune findings. A follow-on cerebral spinal fluid study examining metabolomics and immune factors is underway by Simmaron and Columbia.

The Atypical Subset Study

Peterson’s Atypical Subset Opens New View of ME/CFS in Columbia/Simmaron Publication

Advocate and Messenger

Dr. Lipkin is one of a very few ME/CFS researchers to aggressively advocate for this disease, and he acknowledged the ME/CFS community for its work.

“The pace of research has increased, thanks largely to advocacy by the ME/CFS community and the generous support of the Hutchins Family Foundation. We are grateful to NIH for recognizing the potential of this ME/CFS CRC to capitalize on this momentum, bringing together the very best clinical and scientific talent and technology to do work needed to turn a corner on this disease.” Ian Lipkin, MD

The Lipkin team will also connect with the key players in the digital online media (The Solve ME/CFS Initiative, ME Action and the Microbiome Project) to disseminate the group’s work, engage patients and break up the stigma surrounding ME/CFS.

“One of our goals is to dissolve barriers between scientists, clinicians, individuals with ME/CFS, and advocates. By connecting with the global digital ME/CFS community, we aim to increase the visibility and reduce the stigma of what many have described as an invisible population.” Dana March, assistant professor of Epidemiology at the Mailman School and deputy director and administrator of CfS for ME/CFS.

Simmaron Research is proud of its longstanding collaboration with Columbia, and we congratulate all of the collaborators, patients and advocates who worked hard for years to make this landmark investment by NIH in ME/CFS research centers happen.