2 Video: Jorge Benach On Tickborne Disease At Stony Brook

I came across this video on Youtube which I haven't seen mentioned elsewhere. It is a presentation by Dr. Jorge Benach on tickborne diseases, mostly focused on cases in New York State and much of it on Lyme disease - but there is also discussion on tickborne diseases in a more general sense as well.

I watched the video and made a note on topics of discussion during various points of time during the presentation which may be of interest to others.

Note that it is a little over an hour long, but you can skip the first three minutes as they are only an introduction. The last fifteen minutes are dedicated to a question and answer session with the audience - including one person who walked out because she was not satisfied with Dr. Benach's response.

[Time: 1:06:41]




11:39 Benach discusses Lone Star tick as primary tick on Long Island and that the number of cases of Lyme disease are going down in Eastern Long Island - possibly due to this tick's expansion.

16:33 Lifestyle of Ixodes tick described.

23:17 Early Babesia microti case on Long Island identified in 1970's - opens discussion on Babesiosis. Risk categories: over 50, elderly, asplenic, immunosuppressed, and/or alcoholism history.

29:00 Beginning of Lyme disease discussion... history of discovery, use of dark field microscopy for detection; electromicroscopy.

36:12 60% of patients have EM rash that is noticed. 40% do not.

37:00 Disseminated Lyme - Neuroborreliosis -20%, Cardiac disease- 5-10%, Arthritis - 60%

37:20 Secondary Disseminated symptoms - refractory to treatment - Benach does not understand what happens with chronic Lyme disease patients. Audience member brings up infection-related damage, Benach agrees with him that this is a problem - then goes back to discussing acute Lyme disease.

39:40 A rash that enlargens is clearly an EM rash. This is key to early diagnosis with a rash.

40:20 Multiple EM rash is sign of disseminated Lyme disease and requires IV or parenteral antibiotics.

40:57 Discusses spirochetes affecting the CNS and how it is similar to syphilis, and that a dementia-like form of Lyme disease is controversial. Audience member mentions person who was completely messed up by neurological Lyme disease; had CSF that was positive for Lyme disease and improved with IV treatment.

43:00 Benach thinks neurologic involvement in Lyme disease is underreported.

43:10 Explanation of Bells palsy in a child, says it is very common but not malignant.

43:57 Mentions Lyme arthritis in the classic sense. Discusses symptoms as relapsing and remitting.

44:38 Benach is under impression that most people's cases of Lyme disease are caught early and treated early due to presence of EM rash.

44:50 Epidemiology of Lyme disease in New York State and counties in NY. Benach thinks doctors in some counties are treating Lyme disease and are not reporting their cases to the state any more - they are "Lyme tired". For other counties, there is active surveillance, and the numbers are going up as more cases are new to their area.

47:00 Quip that LD now threatens politicians in Albany.

47:48 Is Lonestar tick driving other ticks away? Maybe… someone needs to study it.

48:13 Audience member asks about birds. Catbirds and robins have ticks, but don't carry a lot because they like the rims near eyes (bare skin). Birds are dead ends for the spirochetes because of their high temperature, according to Benach…

49:30 Start of Q & A session

51:38 Do people have natural immunity to Lyme disease? Benach does not think so - there is universal susceptibility to LD.

53:00 Jury still out on whether or not people have genetic susceptibility to Lyme disease. Hard to know if you are bitten multiple times if you have new instance of disease or preexisting disease because Lyme disease can last for 30 (possibly more) years in the human body.

54:40 No known existence of antibiotic resistant Lyme disease. Does he rule it out completely? No. But he states Borrelia are genetically challenged and have so few genes they need them to do housekeeping; they have a very small genome. He says there is no presence of those genes and he is 90% sure there is no antibiotic resistance.

57:09 Vaccine discussion - brief.

58:00 Pesticide soaked cotton balls used to fight ticks locally. (Damminix)

1:00 Opinion on prolonged chronic Lyme IV treatment: If  my child or I myself had a very strong titer for Lyme disease, I would use antibiotics for as long as it did good. If I did not have a very strong titer, then I would be reluctant to use antibiotics due to side effects.

Recurring arthritis and neurological manifestations come with strong serology according to Benach.

Benach leaves the audience with a confusing opinion: On one hand, he states he would not take antibiotics long term. On the other, he states that if he continued to be sick in the presence of strong serology then he would take antibiotics.

1:05 IgM doesn't drop over time in Lyme disease. We cannot culture Lyme disease easily, doesn't grow well in vitro - it is very slow growing. Only mycobacteria divides more slowly. You need 5 weeks to culture Borrelia. Benach's implication is no one would wait for those results - test is too difficult; takes too long.

More info. on Dr. Benach's research:
http://www.mgm.stonybrook.edu/benach/index.shtml


Comments:

One of my main comments for now (I may add more later) is that I think Dr. Benach is wrong about the birds.

I found this article: http://news.discovery.com/animals/migrating-birds-lower-body-temperature.html

Migrating birds can easily carry Borrelia spirochetes because their average daytime temperature is around 42.5C and goes down to 33C at night - the birds temporarily have hypothermia. They do this to save energy during long trips.

While some strains of Borrelia are sensitive to the birds' higher temperature range, some birds are actually conducive of supporting Borrelia spirochetal infections. Catharus fuscescens is one example.

See: http://jmm.sgmjournals.org/content/47/10/929.full.pdf

B. garinii, at 41C has the highest growth temperature on record. However, just because Borrelia stop growing doesn't indicate it is not present. Under varying temperature conditions, some Borrelia may be able to survive.

Another comment is that Dr. Benach mentions that Borrelia burgdorferi does not show signs of antibiotic resistance or genes for antibiotic resistance mechanism.

However, there are some spirochetes which have been resistant to erythromycin, and there is now some evidence of an antibiotic resistance mechanism in Bb: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000009

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0 New Ehrlichiosis Strain Causing Disease In Sweden

Researchers at the University of Gothenburg's Sahlgrenska Academy have discovered a brand new tick-borne infection. Since the discovery, eight cases have been described around the world, three of them in the Gothenburg area, Sweden.

The disease-causing agent is bacteria known as Neoehrlichia mikurensis. This bacterium was identified for the first time in Japan in 2004 in rats and ticks but had never before been seen in Sweden in ticks, rodents or humans.

One notable symptom of the disease - alongside typical tickborne infection symptoms such as fever and diarrhea - is the development of deep vein thrombosis.

Read more here: http://www.sciencedaily.com/releases/2011/12/111206131404.htm

Comment:

It's always prudent to keep in mind that Borrelia burgdorferi (as well as other Borrelia) are not the only bacteria that can be transmitted by ticks. Many different diseases can be contracted - bacteria, viral, and protozoal. One can be bitten by a tick and infected by a coinfection and not be infected by Borrelia at all - though it is more likely in many parts of the world for the tick to be infected with Borrelia as well.

The rule of "if the tick was on me for less than 24 hours, I'm probably okay" is not a real rule. The twenty-hour hour minimum for Lyme disease transmission time was based on limited research, and research on transmission time for many coinfections has indicated far less attachment time is needed for an infection to develop.

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0 Review Of The 2011 Lyme and Tick-Borne Diseases National Conference

In October 2011, a national conference on Lyme and tick-borne diseases was held in Philadelphia by Columbia University and the Lyme Disease Association.

Here is a brief overview of the topics presented:

• Dr. J. William Costerton’s riveting talk on “The Role of Biofilms in Chronic Bacterial Infections” reviewed the history of the discovery of biofilms, demonstrating that these biofilms enable micro-organisms to resist host defenses and antibiotics, enabling infections to become chronic.
• Dr. Eva Sapi’s talk on “Killing Borrelia – an impossible job?” addressed various mechanisms associated with Borrelia burgdorferi that may help it to survive despite antibiotic treatment.
• Dr. Jason A. Carlyon’s talk focused on Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis (HGA). This emerging tick-borne pathogen demonstrates stealth trickery, enabling it to avoid and even subvert immune cells.
• Dr. Richard Marconi’s talk on “C-Di-GMP” described research demonstrating that the cyclic nucleotide, c-di-GMP, plays a critical role in regulating several important cellular processes.
• Dr. Chris Earnhart’s talk described work developing a novel next-generation Lyme disease vaccine based on outer surface protein C. Osp C is expressed by all Bb species and strains and is expressed in the human host for several weeks before being down-regulated.
• Dr. Robert S. Lane gave a brief overview of his research team's long-term studies of the ecology and epidemiology of Lyme disease in California, and then summarized some exciting recent findings regarding the genospecies and genotypes of Borrelia burgdorferi s. l. that infect the western black-legged tick and humans in this region.
• Dr. Karen Newell Rogers presented a talk about novel ways to target chronic inflammation and chronic immune activation among patients with chronic Lyme disease. The primary controversy with Lyme disease has been whether the disease is the result of long-lasting bacterial infection or whether long-term symptoms result from a post-infectious, uncontrolled autoimmune response.
• Dr. Robert Yolken’s talk on “Infections and Human Neuropsychiatric Diseases” focused on the Stanley Center’s work at Hopkins which has examined infectious triggers of psychosis.
• Dr. Josep Dalmau’s talk on “The Clinical Spectrum and Cellular Mechanisms of Autoimmunity in NMDA and other synaptic receptors”. His pioneering work studying anti-NMDA receptor encephalitis shows how an immune response triggered by a tumor (e.g., ovarian teratoma) or perhaps an infectious process, results in antibodies that can attack critical receptors and synaptic proteins in the Central Nervous System involved in memory, behavior, cognition, and psychosis.
• Dr. John Aucott’s talk on “Early Lyme disease” reported from the SLICE prospective cohort and his Maryland studies.
• Dr. Reinhard K. Straubinger's talk on “Canine and Equine Lyme Borreliosis” focused on Lyme borreliosis in animals, especially in dogs and horses.
• Dr. James Moeller presented a talk on “Immunologic aspects of neuropsychiatric illness: Lyme disease as model”.
• Dr. Brian Fallon presented a talk on “Models of Chronic Lyme Disease”. The talk started with a review of the terms that refer to chronic symptoms and recommendations on how the the IDSA’s definition of Post-treatment Lyme Syndrome could be improved. This talk reviewed the evidence regarding models of persistent infection and/or persistent immune activation.
• Dr. Andrew Walter reported on Ehrlichiosis and Hemophagocytic Lymphohistiocytosis (HLH) in cases of children diagnosed in Delaware.
• Dr. Andrea Gaito provided an update on the clinical evaluation and treatment of Lyme Arthritis from an autoimmune perspective. Lyme arthritis occurs in sixty percent of patients with untreated Lyme disease.
• Dr. Ingeborg Dziedzic presented an interesting (and at times entertaining) overview of how Lyme disease impacts the eye, emphasizing that the eye is in part like the skin and in part like the brain.
• Dr. Vijay Thadani presented an overview of seizures and non-epileptic seizures, showing videos of both. Brain infections such as Lyme disease can lead to the development of epilepsy.
  
• Dr. Steve Bock addressed complementary and integrative medicine approaches to the treatment of chronic Lyme disease.
• Dr. Elizabeth Maloney addressed studies of antibiotic treatment of Lyme disease, providing a thoughtful and critical review of the literature to identify lessons, gaps, and future research needs.

READ MORE - Full Presentation Information Here:
2011 Lyme and Tick Borne-Diseases National Conference Summary Report

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0 Reader Mail Bag: What Lyme Disease Research Is Needed?

A reader, Misty, recently commented on my request for topics for discussion this week:

"I like all your ideas for topics - and hope you'll be able to continue posting. I love your "blog - it is one of the most sane Lyme sites on the web, if not the most sane and balanced.

What I wonder is - do we have enough information and diagnostic tools to be able to design useful studies on Lyme?

- we can't tell reliably who has it or doesn't
- the manifestations of Lyme in each person can be different and based on complications of co-infections and the genetic predisposition of the person to exaggerated inflammatory response
- then there is the pesky post-Lyme-Syndrome/Chronic Lyme issue of whether there is infection or post-infection inflammation

So, you may have covered it already, but I am interested in hearing about ideas for scientific studies - where is the research most needed?"

thanks,
misty

Well, Misty, addressing your questions and points:

I think we can design useful studies on Lyme disease even without being capable of accurately testing every patient who has Lyme disease. Improving serological testing and being able to accurately assess whether one has or does not have Lyme disease at present are only two pieces of the bigger picture, and there are more angles from which to approach the Lyme disease problem.

Research that can be useful in gaining a better understanding of what Borrelia burgdorferi and other Borrelia do is important to understanding how to effectively diagnose and treat infection and perhaps distinguish between patients who are affected by Lyme disease and those who are affected by a different condition.

Here's a few ideas I have on what to consider for further study:

1) Do a comparative study which looks at the proteins in the CSF of patients with chronic Lyme disease versus patients with late stage untreated and patients with acute Lyme disease.

Earlier this year, we've seen the study where hundreds of proteins were found in the CSF of patients with post-treatment Lyme disease symptoms and compared against patients with Chronic Fatigue Syndrome. The protein profile for each group was different, and each group's profile differed from healthy controls.

Let's take this study one step further, and see if there is a protein profile that distinguishes between patients who were designated as suffering from post-treatment Lyme disease symptoms and those who are  late stage and newly infected.

The outcome of this study may shed some light on what markers are present for different stages of the disease. Having different markers for different stages of the disease may help guide better test research and development.

References:
Steven E. Schutzer, Thomas E. Angel, Tao Liu, Athena A. Schepmoes, Therese R. Clauss, Joshua N. Adkins, David G. Camp II, Bart K. Holland, Jonas Bergquist, Patricia K. Coyle, Richard D. Smith, Brian A. Fallon, Benjamin H. Natelson. Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017287

2) Conduct longer term in vivo GFP and/or iRFP studies on mice and other mammals.

In this GFP protein study on mice, spirochetes' motion was monitored in vivo rather than in vitro (go to link to watch video of spirochetes attaching to endothelial walls). Rather than study it for as short a period of time as was done, a longer time frame for study as well as multiple studies over time in the same hosts would be educational.

With longer term imaging, one can see if spirochetes become intracellular and for how long. One can see which parts of the body they travel to and see them hide in immunological niches. One can see how likely different strains are to enter the CNS and how quickly they enter the CNS post-inoculation. (We already know specific strains are more neurotropic than others, but how serious a problem is this for the host? Does it depend on the host animal?)

Perhaps a GFP or iRFP study on mice could also be combined with an antibiotic treatment study. If we can trace the activity and polymorphic state of spirochetes in vivo, then we can see if antibiotics of specific types can affect "cyst"-like forms of spirochetes in vivo, too.

3) Repeat Klempner intracellular studies with a longer observation time and longer ceftriaxone infusion.

Also - give two weeks' ceftriaxone then provide no treatment for a few months. Try a different duration of ceftriaxone. Recheck the host animal for signs of infection at 3 months, 6 months, a year, then two years.

How can an in vivo study of this issue be completed?

References:
Kostis Georgilis, Monica Peacocke, and Mark S. Klempner. Fibroblasts Protect the Lyme Disease Spirochete, Borrelia burgdorferi, from Ceftriaxone In Vitro. Journal of Infectious Diseases. Vol. 166, pp. 440-444. 1992.
Mark S. Klempner, Richard Noring and Rick A. Rogers. Invasion of Human Skin Fibroblasts by the Lyme Disease Spirochete, Borrelia burgdorferi. The Journal of Infectious Diseases. Vol. 167, No. 5 pp. 1074-1081. May 1993. http://www.jstor.org/pss/30112679

4) Use new maltodextrin enhanced imaging study in animal subjects (and later people) to see where bacteria is.

This is a very new imaging method, but the advantages are clear: Maltodextrin is viewed by pathogenic bacteria as food, whereas regular mammalian cells (human, mouse, other) and even commensal or friendly bacteria in the gut do not view maltodextrin as food and they work to eliminate it.

With the addition of a maltodextrin contrast agent, one should be able to see where pathogenic bacteria are present in the body in vivo and do so safely.

And there's more:

"In experiments using a rat model, the researchers found that the contrast agent accumulated in bacteria-infected tissues, but was efficiently cleared from uninfected tissues. They saw a 42-fold increase in fluorescence intensity between bacterial infected and uninfected tissues. However, the contrast agent did not accumulate in the healthy bacterial microflora located in the intestines. Because systemically administered glucose molecules cannot access the interior of the intestines, the bacteria located there never came into contact with the probe. 

They also found that the probes could detect as few as one million viable bacteria cells. Current contrast agents for imaging bacteria require at least 100 million bacteria, according to the researchers. 

In another experiment, the researchers found that the maltodextrin-based probes could distinguish between bacterial infections and inflammation with high specificity. Tissues infected with E. coli bacteria exhibited a 17-fold increase in fluorescence intensity when compared with inflamed tissues that were not infected."

All of these items in bold are of particular interest to those wishing to see where Borrelia burgdorferi is present during infection. If - as a number of researchers have stated - Borrelia burgdorferi are actually low in number and produce high amounts of inflammation in tissues, maltodextrin contrast should be able to confirm this finding. We'd also have a better idea of where the bacteria is in vivo without having to do a tissue biopsy, and be able to detect biofilms if any have formed.

Initial studies should be conducted on animal models, and if proven safe and effective, I see no reason why human studies wouldn't follow.

References:
Xinghai Ning, Seungjun Lee, Zhirui Wang, Dongin Kim, Bryan Stubblefield, Eric Gilbert, Niren Murthy.Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nature Materials, 2011; DOI: 10.1038/nmat3074
Scientific American: http://blogs.scientificamerican.com/lab-rat/2011/07/25/making-bacteria-visible/
Science Daily: http://www.sciencedaily.com/releases/2011/07/110718121605.htm
Nature: http://www.nature.com/nmat/journal/v10/n8/full/nmat3074.html

5) Complete more treatment studies on patients with documented late stage Lyme disease and coinfections such as Ehrlichiosis and Babesiosis.

If it's problematic to differentiate between those who suffer from a chronic, persisting infection and those who suffer from an autoimmune disorder, then circumvent the issue by finding people who are truly late stage, untreated Lyme disease patients who have coinfections and study how long it takes for them to get well on combination treatments.

Many Lyme patient activists promote more studies for those of us suffering from persistent post-treatment symptoms when perhaps it is more advantageous to first push for the study of patients who have never been treated and have evidence of late stage symptoms. There are far more studies on acutely infected patients than there are on late stage patients, and this needs to be addressed, I think, in order to bridge the gap between acute cases and post-treatment cases (chronic Lyme; PLDS) and work past any controversy.

6) Run comparative studies on all labs which conduct Lyme disease tests - C6/ELISA and Western Blot IgM and IgG.

Test all existing labs for sensitivity and specificity for various strains including Borrelia lonestari and miyamotoi - include the relapsing fever Borrelias. It would be informative to know how all the labs perform and why they receive the results they do.

These are just some of the ideas I have on studies which could be conducted that give us more answers.

Regardless of these suggestions, one has to be aware of the limitations of using animal studies to model what happens in human infection. For one thing,  even non-human primate studies may not show evidence of a Borrelia burgdorferi brain infection, even with an N40 strain of Bb which is neurotropic. For another, mice do not get brain infections and are thus a poor model for studying neuroborreliosis.

References:
Ramesh, G., Borda, J., Dufour, J., Kaushal, D., Ramamoorthy, R., Lackner, A., & Philipp, M. (2008). Interaction of the Lyme Disease Spirochete Borrelia burgdorferi with Brain Parenchyma Elicits Inflammatory Mediators from Glial Cells as Well as Glial and Neuronal Apoptosis. American Journal Of Pathology, 173 (5), 1415-1427 DOI: 10.2353/ajpath.2008.080483
Diego Cadavid, Tim O'Neill, Henry Schaefer, and Andrew R. Pachner (2000). Localization of Borrelia burgdorferi in the Nervous System and Other Organs in a Nonhuman Primate Model of Lyme Disease.Laboratory Investigation, 80 (7), 1043-1054

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0 News: In Wisconsin, Illnesses spread by ticks on rise

The Wisconsin Rapids Tribune has this article on tap today:

Illnesses spread by ticks on rise

Excerpts:

Consistent testing and an increase in deer ticks are driving up the number of tick-borne illnesses reported annually in Wisconsin, health officials said.

Statewide, cases of the bacteria infections anaplasmosis and ehrlichiosis -- both spread by deer ticks -- increased 70 percent from 2009 to 2010, when 546 cases were reported, according to state data.

"It's nice to be able to pick (anaplasmosis and ehrlichiosis) up, so a patient can be properly treated," said Diep Hoang Johnson, an epidemiologist for Wisconsin's Division of Public Health. "If lyme disease (tests) come back negative, they may not get treated and they may have one of these diseases."

and

"Marx said the increase in tick diseases other than lyme likely is because of more efficient testing and health care providers' improved efforts to report the illnesses."

Comments:

It's important to keep in mind that not every tick bite leads to a case of Lyme disease, and a negative Lyme disease test result does not necessarily mean the patient does not have Lyme disease (antibodies may not have been present at the time the test was taken) - nor does it indicate what other tickborne infections a person may have such as Ehrlichiosis or Babesiosis (as well as a few viruses which are spread by tick bites).

It's important for doctors and patients to familiarize themselves with the range of tickborne infections which are out there and be aware of the symptom spectrum for all them, as well as for doctors to take a detailed history from patients to see where they have traveled and resided to determine which tickborne diseases they are at greater risk of contracting. This provides a starting point for which coinfections to test for - but is by no means definitive as these diseases spread and even change in geographic location and density.

Read more of this news article at: http://www.wisconsinrapidstribune.com/article/20110828/CWS0101/108280518/Illnesses-spread-by-ticks-rise

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