1 Persistence of Borrelia Infection After Antibiotic Use In Mice

For the random passerby who types "is chronic lyme real" into Google, here is more data to consider, coming from Columbia University.

Credit to: Dr. Brian Fallon, Lyme and Tick-borne Diseases Research Center, Columbia University.
Link source as of Feb. 17, 2011: http://www.columbia-lyme.org/research/keyarticles.html

Persistence of Borrelia burgdorferi in mice after antibiotic therapy.

Two studies have recently been published which reveal that Bb may persist in the mouse despite antibiotic therapy. These studies support much earlier work by Straubinger et al in the dog model (1997) and Bockenstedt et al (2002) in the mouse model. Bockenstedt et al (2002) showed that Bb persistence can occur after antibiotic treatment and that these spirochetes could be acquired by ticks (xenodiagnosis) but that the infected ticks could not transmit infection to naïve hosts – suggesting that the spirochetes were attenuated in that they had become non-infectious. Straubinger et al (1997) had shown that even after 30 days of antibiotic treatment, Bb spirochetes could be demonstrated in 3/12 dogs by culture, and DNA could be demonstrated by PCR in 9/12 dogs long after treatment.

More recently, Hodzic et al from UC Davis in California reported in Antimicrob Agents Chemother. (2008;52(5):1728-36) a study which examined the effectiveness of antibiotic treatment using ceftriaxone or saline for 1 month. Mice were treated either early in the infection (3 weeks) or later (4 months). Tissues were tested by immunohistochemistry, PCR, culture, transplantation of allografts, and xenodiagnosis at 1 and 3 months after treatment. Tissues from the mice treated with antibiotics were culture negative, but tissues from some of the mice remained PCR positive and intact antigen-positive organisms with spirochetal morphology were visualized in collagen-rich tissues. Xenodiagnosis demonstrated that uninfected larval ticks after feeding on the antibiotic-treated mice were able to acquire spirochetes (confirmed by PCR) and then transmit these spirochetes to naïve SCID mice which became PCR positive but culture negative. This study therefore demonstrated that antibiotic treatment in the mouse model does not result in eradication of the Bb spirochetes and that some of these spirochetes were infectious, although attenuated in activity.

Yrjanainen et al from Univ of Turku in Finland reported in J Infectious Disease (2007; 195(10):1489-96) a study which examined whether anti-tumor necrosis factor-alpha would have a beneficial effect on Bb-infected mice. C3H/He mice were infected with B. garinii A218 or B. burgdorferi sensu stricto N40. In study 1 (with B. garinii) and in study 2 (with Bb SSN40), 2 weeks after infection, 10 mice were treated with ceftriaxone only for 5 days and 10 mice were treated with anti-TNF-alpha only. In another group of 10 mice, anti-TNF was added simultaneous to the ceftriaxone at 2 weeks after infection while in another group of 10 mice anti-TNF was added at 6 weeks after infection (ie, 4 weeks after ceftriaxone). Finally, a fifth group of mice was treated with saline as a sham treatment. For the group that received ceftriaxone only, no samples were positive by culture or by PCR at 2 weeks after infection. However, among those mice treated with anti-TNF-alpha either at 2 weeks or 6 weeks after infection, spirochetes grew from one-third of the mice. Contrary to earlier findings by Bockenstedt et al (2002) in which the spirochetes detected after antibiotic treatment were attenuated in activity, the recovered spirochetes in this study did not appear to be attenuated, as ceftriaxone sensitivity rates, plasmid profiles, and virulence rates were similar to those of bacteria used to infect the mice. This study demonstrated that a portion of B. burgdorferi-infected mice still have live spirochetes in their body, which are activated by anti-TNF-alpha treatment.

Commentary

 These two studies demonstrate that Bb spirochetes can persist in the mouse after ceftriaxone therapy. The Finnish study was remarkable in that culture and PCR were negative after ceftriaxone but, after additional treatment with anti-TNF-alpha, viable spirochetes were recovered. TNF is a pro-inflammatory cytokine which, when blocked, typically results in a reduction in clinical inflammation; for this reason, such treatment is used for patients with rheumatoid arthritis. To the surprise of the authors, viable spirochetes were recovered in these PCR- and culture-negative mice after TNF blocking treatment was given. Also interesting is that anti-TNF treatment did not result in the expected finding of a reduction of joint swelling.

The Finnish study was the first study to demonstrate that immunomodulatory treatment of animals infected with Bb could convert them from culture negative to culture positive. The California study was remarkable in that only tick-feeding was capable of extracting infectious but non-replicating attenuated spirochetes; without having done that step of xenodiagnosis and then transferring the tick to feed on naïve SCID mice, the authors’ conclusion would have been that infectious spirochetes do not persist in the mouse model as culture was negative. The authors further concluded that negative culture and PCR can not be relied upon as markers of treatment success.

We do not know the extent to which these findings can be translated to the human situation. Nevertheless, the activation of infectious spirochetes after anti-TNF therapy in mice should alert clinicians to the possibility that anti-cytokine therapy may result in a similarly increased risk of activating latent infection among patients with a history of treated Lyme disease. At this point, we do not know whether attenuated spirochetes are capable of inducing illness-symptoms in mice or humans; while it is possible that spirochetal mRNA may be producing surface lipoproteins that stimulate systemic symptoms, this hypothesis needs to be tested in the next phase of this important research.

BAFallon, MD

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So here is food for thought. I would like to see these studies repeated by someone else for confirmation of these findings. Of course, this is in mice and not in humans, but I've said before, mice have been used by researchers for ages now to determine disease courses and treatment possibilities in humans. 


One thought after this is that if there is an immune dysregulation element to persistent infection, it may be harder to treat that aspect of it if treatment itself activates a latent infection. 


One next step for discovering how Borrelia burgdorferi persists would be to carry out  xenodiagnosis in human hosts based on the first study above - of which a similar study, Searching for Persistence of Infection in Lyme Disease, is being conducted by the NIH. This study has been received with some element of controversy, though - and will be discussed in a future post.

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0 The Friday Four

Bringing you four links on Friday you may be interested in and don't want to miss...

1. Takes a licking, keeps on ticking... that's the story of ticks in your washer and dryer.
   
   
   
   
   Okay, I know this isn't news, but it may be to someone and because it is important, I am reposting it here:
   
   Wash and dry clothes at HIGH temperatures after spending time in areas known to harbor ticks.
   
   If you can get clothes that can withstand an hour of being in a dryer on a high temperature setting - all the better.
   
   
   Excerpts from this research include:
   

   "Carroll used a combination of water temperature settings and detergent types to wash the ticks. The majority of lone star ticks survived all the water-detergent combinations with no obvious side effects. Most of the deer ticks lived through the cold and warm water settings as well. But when one type of detergent was used with a hot water setting, only 25 percent of the deer ticks survived.
   
   When it came time to dry, all the ticks of both species died after an hour of tumbling around at high heat. But when the dryer was set to "no heat," about one-third of the deer ticks and more than half of the lone star ticks survived."

2. I know an old lady who swallowed a fly... I don't know why she swallowed that fly... perhaps she'll die?  Hope not.
   
   

   

   Leishmania

   So as the story goes - or this particular variation of it - that sand fly had Leishmania infection, and get this? The Leishmania parasite was also infected with a virus that can trigger a severe response in macrophages, allowing the parasite to do more harm in animal infections
   
   
   
   In humans, the parasite's viral infection may be why some strains of Leishmania in Central and South America tend to cause a disfiguring form of disease that erodes the soft tissues around the nose and mouth
   
   
   How often does this sort of infectious piggybacking go on? This brings more issues to light when discussing polymicrobialism. 
   
   
   We just don't know how all these organisms are interacting - or even that they are there.
   
   
3. On the other hand... Maybe you should hold off on that parasite cleanse. Do you have abdominal pain or symptoms of IBS, celiac disease, MS, asthma, or food allergies? Thinking of doing a parasite cleanse? You may just want to hold off on that cleanse, depending on what is bugging you: Research is being done on the benefits of certain parasites in human hosts with the above conditions.
   
   
   
   The treatment used is called Helminthic therapy, where patients are inoculated with specific intestinal parasitic nematodes and monitored for improvements in their conditions.
   
   Helminthic therapy is based on the hygeine hypothesis. The hygiene hypothesis proposes that appropriate immune response is in part learned by exposure to these microorganisms and parasites, and in part regulated by their presence. In industrialised nations, humans are exposed to somewhat lower levels of these organisms. The development of vaccines, hygienic practices, and effective medical care have diminished or eliminated the prevalence and impact of many parasitic organisms, as well as bacterial and viral infections. This has been of obvious benefit with the effective eradication of many diseases that have plagued human beings. However, while many severe diseases have been eradicated, humans' exposure to benign and apparently beneficial parasites has also been reduced commensurately.
   
   
4. Women with anemia - low iron levels - need to know this.  Dr. Kathryn Clancy writes a blog with informative medical information in it, and this recent post is no exception.
   
   Remember the old saw about how women have lower iron levels than men and are more likely to have anemia due to menstruation? Well, it looks like bunk. 

Red blood cells (RBC) and hemoglobin (Hg) are positively correlated
with endometrial thickness (from Clancy et al 2006). Click for a closer look.

Dr. Clancy sites studies stating the following:

• The sex difference in iron status in males and females derives from an increase in male iron stores at puberty, not a decrease in female iron stores. This has to do with oxygen transport and testosterone (Bergstrom et al 1995).
  
  
• The main culprit for iron-deficiency anemia (IDA) in men is upper-gastrointestinal bleeding, so when men present with IDA the first thing they do is an endoscopy. When women present with IDA they give her iron supplements and tell her to go home because it's just her ladybusiness. Kepczyk et al (1999) decided to actually do endoscopies on women for whom a gynecological source was diagnosed by a specialist for their IDA. They found a whopping eighty-six percent of these women had a gastrointestinal disease that was likely causing their IDA.
  
  
• Resumption of menses after pregnancy is positively associated with hemoglobin. That iron stores increase once you start getting your period again, indicate again that menses is not having a negative effect on iron stores.

The good doctor's advice to women?

"Ladies, unless you are menorrhagic (bleeding more than 120 milliliters each cycle) your period is not doing you wrong. If you have iron-deficiency anemia and your doctor is insisting it's because you slough off your endometrium from time to time without doing a single test to confirm it, you may want to insist on an endoscopy. It could save your life."

Have a good weekend, readers... I am still working on my post-dated citations, so expect to see more posts in the meantime before that list is published.

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0 Quiz Time: Logo Answer Key

So though I know many of you viewed the new Camp Other logo, you didn't take up the challenge of commenting on the quiz post. So I have provided the stumped with an answer key - as long as this logo is in use, you can look here to find out who is in it and what odd touches I added...

I wonder what a party would be like if we had all these guys under one tent... Too bad that some of them are dead as of this writing - we'll never know. I would have liked to have been a fly on the wall of this tent if it were ever a reality. Anyway, below is a list of who is who - plus the three objects I mentioned in the last post about this logo.

1. Richard Feynman (1918-1988) was an American physicist who won the Nobel Prize in 1965 for "for fundamental work in quantum electrodynamics, with deep-ploughing consequences for the physics of elementary particles". Physicists and physics students will understand that more than anyone else. Outside of his Nobel prize, Feynman was memorable for his physics classes at Caltech, his work on The Manhattan Project, his testimony on the Space Shuttle Challenger disaster, for his skill as a drummer and artist, his interest in genetics, and for his attempts to visit formerly Soviet-controlled Tuva.
   
   One thing I really liked about Feynman: Feynman has been called the "Great Explainer". He gained a reputation for taking great care when giving explanations to his students and for making it a moral duty to make the topic accessible. His guiding principle was that if a topic could not be explained in a freshman lecture, it was not yet fully understood.
   
   
2. Bill Nye (The Science Guy) is a science educator, comedian, television host, and mechanical engineer. He is best known as the host of Disney's science education show, Bill Nye the Science Guy (1993-1997). He began his career at Boeing and developed a hydraulic pressure resonance suppressor still used in the 747.
   
   
   
   
   He went on to do aerospace consulting, was a comedian on the show, Seattle, Almost Live!, created The Eyes of Nye PBS science show for adults, has been a lifeline expert on Who Wants To Be A Millionaire, and had clips of his show in the popular (over 2 million hits!) Symphony of Science series.
   
   See Bill Nye, Carl Sagan, and Richard Feynman clips in this Symphony of Science mashup, We Are All Connected:
   
   
   
3. Susumu Tonegawa 利根川 進 is a Japanese scientist who won the Nobel Prize for Physiology or Medicine in 1987 for his discovery of the genetic mechanism that produces antibody diversity. Tonegawa is best known for elucidating the genetic mechanism in the adaptive immune system. To achieve the diversity of antibodies needed to protect against any type of antigen, the immune system would require millions of genes coding for different antibodies, if each antibody was encoded by one gene. Instead, as Tonegawa showed in a landmark series of experiments beginning in 1976, genetic material can rearrange itself to form the vast array of available antibodies.
   
   
4. Wayne Rogers (as "Trapper John McIntyre") is an actor who is best-known for playing "Trapper John", a doctor on M*A*S*H who was tent mates with Alan Alda's "Hawkeye Pierce". Many years ago, Wayne was asked to sign a contract agreeing not to engage in "objectionable behavior" while working on the set of the show or otherwise risk being fired, and refused to unless the directors and production company were held to the same standard.
   
   
5. Barbara McClintock (1902-1992) was the 1983 Nobel Laureate in Physiology or Medicine, was an American scientist and one of the world's most distinguished cytogeneticists. McClintock received her PhD in botany from Cornell University in 1927, where she was a leader in the development of maize cytogenetics. Her work was groundbreaking: she developed the technique for visualizing maize chromosomes and used microscopic analysis to demonstrate many fundamental genetic ideas, including genetic recombination by crossing-over during meiosis—a mechanism by which chromosomes exchange information. She produced the first genetic map for maize, linking regions of the chromosome with physical traits, and demonstrated the role of the telomere and centromere, regions of the chromosome that are important in the conservation of genetic information.
   
   
6. Carl Sagan (1934-1996) was an American astronomer, astrophysicist, cosmologist, author and science popularizer and science communicator in the space and natural sciences.
   
   
   
   During his lifetime, he published more than 600 scientific papers and popular articles and was author, co-author, or editor of more than 20 books. In his works, he advocated skeptical inquiry and the scientific method. He pioneered exobiology and promoted the Search for Extra-Terrestrial Intelligence (SETI).
   
   Sagan became world-famous for his popular science books and for the award-winning 1980 television series Cosmos: A Personal Voyage, which he narrated and co-wrote. A book to accompany the program was also published. Sagan also wrote the novel Contact, the basis for the 1997 film of the same name.
   
   
7. Elizabeth Blackburn is an Australian-born American biological researcher at the University of California, San Francisco, who studies the telomere, a structure at the end of chromosomes that protects the chromosome. Blackburn co-discovered telomerase, the enzyme that replenishes the telomere. For this work, she was awarded the 2009 Nobel Prize in Physiology or Medicine, sharing it with Carol W. Greider and Jack W. Szostak. She also worked in medical ethics, and was controversially dismissed from the President's Council on Bioethics.
   
   
8. Alan Alda (as "Hawkeye Pierce")  is an American actor, director and screenwriter. A five-time Emmy Award and six-time Golden Globe Award winner, he is best known for his role as Hawkeye Pierce in the TV series M*A*S*H. During the 1970s and 1980s, he was viewed as the archetypal sympathetic male, though in recent years, he has appeared in roles that counter that image. He is currently a Visiting Professor at the Stony Brook University School of Journalism.
   
   Alda's prominence in the enormously successful M*A*S*H gave him a platform to speak out on political topics, and he has been a strong and vocal supporter of women's rights and the feminist movement. He co-chaired, with former First Lady Betty Ford, the ERA Countdown campaign. Alda has also played Nobel Prize-winning physicist Richard Feynman in the play QED, which has only one other character. Although Peter Parnell wrote the play, Alda both produced and inspired it. Beginning in 2004, Alda was a regular cast member on the NBC program The West Wing, portraying Republican U.S. Senator and presidential candidate Arnold Vinick, until the show's conclusion in May 2006. It was not until 2004, after a long distinguished acting career, that Alda received his first Academy Award nomination, for his role in The Aviator.
   
   In 2005, Alda published his first round of memoirs, Never Have Your Dog Stuffed: and Other Things I've Learned. Among other stories, he recalls his intestines becoming strangulated while on location in Chile for his PBS show Scientific American Frontiers, during which he mildly surprised a young doctor with his understanding of medical procedures, which he had learned from M*A*S*H.
   
   
9. Ada E. Yonath עדה יונת ( pronounced [ˈada joˈnat]) is an Israeli crystallographer best known for her pioneering work on the structure of the ribosome. She is the current director of the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly of the Weizmann Institute of Science. In 2009, she received the Nobel Prize in Chemistry along with Venkatraman Ramakrishnan and Thomas A. Steitz for her studies on the structure and function of the ribosome, becoming the first Israeli woman to win the Nobel Prize out of nine Israeli Nobel laureates, the first woman from the Middle East to win a Nobel prize in the sciences, and the first woman in 45 years to win the Nobel Prize for Chemistry. However, she said herself that there was nothing special about a woman winning the Prize.
   
   Yonath focuses on the mechanisms underlying protein biosynthesis, by ribosomal crystallography, a research line she pioneered over twenty years ago despite considerable skepticism of the international scientific community. Ribosomes translate RNA into protein and because they have slightly different structures in microbes, when compared to eukaryotes, such as human cells, they are often a target for antibiotics.
   
   Additionally, Yonath elucidated the modes of action of over twenty different antibiotics targeting the ribosome, illuminated mechanisms of drug resistance and synergism, deciphered the structural basis for antibiotic selectivity and showed how it plays a key role in clinical usefulness and therapeutic effectiveness, thus paving the way for structure-based drug design.
   

The three objects/items I mentioned, from left to right:

1. Behind Richard Feynman is a sepia-toned photograph of Lida Mattman near her microscope on the tent wall.
   
   Lida Mattman (1912-2008) graduated with a M.S. in Virology from the University of Kansas and a Ph.D. in Immunology from Yale University. Mattman has taught Immunology, Microbiology, Bacteriology, Virology and Pathology. She worked for 35 years in these fields at various schools and institutions including Harvard University, Howard Hughes Institute, Oakland University and Wayne State University. Mattman developed a new method for culturing B. burgdorferi from patients with chronic Lyme disease. In 1998 she was nominated for the Nobel Prize in Medicine. She authored the book Cell Wall Deficient Forms: Stealth Pathogens.
   
   
2. On the floor in front of Bill Nye is an oscilloscope modified so one can play Tetris on it. Yes, it is real!:
   
   
   
3. On Alan Alda's head is a yellow finch that is one of the finches Charles Darwin identified in the Galapagos Islands.

I was hoping for more participation in comments, and I intend to quiz you in future posts about "what is in this picture" - however, I warn you that those quizzes may prove to be more challenging than this one!

Carl Sagan should have been the obvious one to answer even if you wrote nothing else, since I have mentioned him a number of times on this blog. Since it's The Swamp from M*A*S*H, I thought at least some of the old school would get Alan Alda and Wayne Rogers.

Well, you'll have another chance in the future to participate in other game posts - provided I am well enough to keep writing. Hope you learned something interesting from this one!

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0 Quiz Time! Who's in the logo?

Edit: I'm really surprised you folks are quiet on this one... I'm going to delay releasing my next post and give this another 24 hours for you to guess who's in the new Camp Other logo. 

Okay, the old logo just wasn't working for me... This one might need a little tweaking, but I think it's mostly the right idea for this blog.

Say goodbye to the old beach tent...

And hello to the new logo above.

So... just for fun: Who is in the new logo?

I'm going to leave this up for 24 hours and see how many of you can identify any or all of the people in The Swamp (that should be a clue, right there - I can't imagine that you won't get at least three right off the bat).

Extra bonus points for noting three items not normally found in The Swap which were added to this image.

On your marks... get set... GO!

HAVE FUN!

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0 Koch's Postulates

Just an FYI... for tales of xenodiagnosis...

http://en.wikipedia.org/wiki/Koch's_postulates

Koch's postulates

From Wikipedia, the free encyclopedia

Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890. Koch applied the postulates to establish the etiology of anthrax and tuberculosis, but they have been generalized to other diseases.

The postulates

1. The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.
2. The microorganism must be isolated from a diseased organism and grown in pure culture.
3. The cultured microorganism should cause disease when introduced into a healthy organism.
4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

However, Koch abandoned the universalist requirement of the first postulate altogether when he discovered asymptomatic carriers of cholera^[1] and, later, of typhoid fever. Asymptomatic or subclinical infection carriers are now known to be a common feature of many infectious diseases, especially viruses such as polio, herpes simplex, HIV and hepatitis C. As a specific example, all doctors and virologists agree that poliovirus causes paralysis in just a few infected subjects, and the success of the polio vaccine in preventing disease supports the conviction that the poliovirus is the causative agent.

The third postulate specifies "should", not "must", because as Koch himself proved in regard to both tuberculosis and cholera,^[2] not all organisms exposed to an infectious agent will acquire the infection. Noninfection may be due to such factors as general health and proper immune functioning; acquired immunity from previous exposure or vaccination; or genetic immunity, as with the resistance to malaria conferred by possessing at least one sickle cell allele.

The second postulate may also be suspended for certain microorganisms or entities that cannot (at the present time) be grown in pure culture, such as prions responsible for Creutzfeldt–Jakob disease.^[3] In summary, a body of evidence that satisfies Koch's postulates is sufficient but not necessary to establish causation.

History

Koch's postulates were developed in the 19th century as general guidelines to identify pathogens that could be isolated with the techniques of the day.^[4] Even in Koch's time, it was recognized that some infectious agents were clearly responsible for disease even though they did not fulfill all of the postulates.^[2][5] Attempts to rigidly apply Koch's postulates to the diagnosis of viral diseases in the late 19th century, at a time when viruses could not be seen or isolated in culture, may have impeded the early development of the field of virology.^[6][7]Currently, a number of infectious agents are accepted as the cause of disease despite their not fulfilling all of Koch's postulates.^[8] Therefore, while Koch's postulates retain historical importance and continue to inform the approach to microbiologic diagnosis, fulfillment of all four postulates is not required to demonstrate causality.

Koch's postulates have also influenced scientists who examine microbial pathogenesis from a molecular point of view. In the 1980s, a molecular version of Koch's postulates was developed to guide the identification of microbial genes encoding virulence factors.^[9]

See also

• Willoughby D. Miller
• Molecular Koch's postulates

References

1. ^ Koch Robert (1893). "Über den augenblicklichen Stand der bakteriologischen Choleradiagnose" (in German). Zeitschrift für Hygiene und Infectionskrankheiten 14: 319–333.doi:10.1007/BF02284324.
2. ^ ^a b Koch Robert (1884). "2 Die Aetiologie der Tuberkulose". Mitt Kaiser Gesundh. pp. 1–88.
3. ^ Inglis TJ (November 2007). "Principia aetiologica: taking causality beyond Koch's postulates". J. Med. Microbiol. 56 (Pt 11): 1419–22. doi:10.1099/jmm.0.47179-0. PMID 17965339.
4. ^ Walker L, Levine H, Jucker M (2006). "Koch's postulates and infectious proteins.". Acta Neuropathol (Berl) 112 (1): 1–4. doi:10.1007/s00401-006-0072-x. PMID 16703338.
5. ^ Koch R (1893). "Ueber den augenblicklichen Stand der bakteriologischen Choleradiagnose". J. Hyg. Inf. 14: 319–33. doi:10.1007/BF02284324.
6. ^ Brock TD (1999). Robert Koch: a life in medicine and bacteriology. Washington DC: American Society of Microbiology Press. ISBN 1555811434.
7. ^ Evans AS (May 1976). "Causation and disease: the Henle-Koch postulates revisited". Yale J Biol Med 49 (2): 175–95. PMID 782050.
8. ^ Jacomo V, Kelly P, Raoult D (2002). "Natural history of Bartonella infections (an exception to Koch's postulate)". Clin Diagn Lab Immunol 9 (1): 8–18. doi:10.1128/CDLI.9.1.8-18.2002.PMID 11777823.
9. ^ Falkow S (1988). "Molecular Koch's postulates applied to microbial pathogenicity". Rev. Infect. Dis. 10 (Suppl 2): S274–6. PMID 3055197.

Further reading

• http://ocp.hul.harvard.edu/contagion/koch.html

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23 What's In A Name: Is Chronic Lyme Real?

"Anyone who has a lot of information, thinks a lot, and by thinking increases his understanding of a situation, will have not less, but more trouble coming to a clear decision. To the ignorant, the world looks simple. ...Once we gather a little information, however, we run into trouble. We ... become more acutely aware [of] what we don’t know. This probably explains why we find so few scientists and scholars among politicians. It probably also explains why organizations tend to separate their information -gathering and decision -making branches. ... to provide decision-makers with only the bare outlines of all the available information so that they will not be hobbled by excessive detail when they are obliged to render decisions."

Dietrich Dorner, The Logic of Failure, 1988

A few weeks ago I was reviewing my stat logs for web traffic and looked at the list of common web searches that people used and ended up finding this blog.

One string of keywords popped out to me and it was simply this: "is chronic lyme real".

Of course, I don't know who they were or where they came from, or what their story is. I wonder if they are another human being suffering with symptoms making their life miserable and asking, "Is this it? Could this be my problem?" or if they were perfectly healthy and stumbled upon some article about chronic Lyme Disease that cast doubt on its existence.

I'll probably never know who it was or their reason for being here. But the question is a good one, and surprisingly not a simple one.

Over the course of time I intend to examine the issue of persistence in Lyme Disease - which is directly tied to this question. But to draw on the quote at top, it's not an easy question to answer in some ways.

I know there are likely to be people reading this at this very moment about ready to throw something at the screen because I wrote that. I can hear you all the way over here, through that mass of Cat-5 cables and 3G networks, saying, "What? What do you mean, 'it's not an easy question to answer'? Of course it is - I'm sick with chronic Lyme disease, you ass, so of course it's real!"

And on the flip side, I can also hear the rare, passing IDSA-guidelines-believer almost audibly shrugging and saying, "Heh. That's easy. Of course chronic Lyme is not real... What was that link I was really looking for? Ah, yes... there is that abstract on Ebola vaccine development..." and moving on.

Now that the initial reaction has passed, though, I'll explain where I was going with my statement if you're still sticking around.

You are? Okay. Then read on, and be prepared for some TLAs (Three Letter Acronyms).

Problems with Naming Conventions 

On the one hand, Chronic Lyme Disease (CLD)* is defined by the Lyme patient community as having chronic and persisting Borrelia bacterial infection. That is a simple baseline definition of CLD.

On the other hand, the Infectious Disease Society of America (IDSA) has been the primary institution in the US (and to some extent, the world) which has set the standard for infectious disease definitions and treatment guidelines for some time.

For the subgroup of the IDSA which set the definition of Lyme Disease and guidelines for its treatment, their current opinion is that Chronic Lyme Disease does not exist, yet they have used the term one way in the past and have defined it differently now.

They believe that people with self-reported symptoms matching those of Lyme Disease are mostly sick with something else other than Lyme Disease, and that a small subset of patients who have had Lyme Disease and are experiencing Lyme-like symptoms after three weeks of antibiotic treatment have a condition known as Post Lyme Disease Syndrome (PLDS).

To use myself as an example, I am what the IDSA (and the cited NEJM article) would consider a "Category 4 Chronic Lyme Disease patient".

According to the IDSA, this means:

"Category 4: Symptoms of unknown cause after antibiotic therapy and resolution of an objective manifestation of Lyme disease. 

Only patients with category 4 disease have post-Lyme disease symptoms. Data from three double-blind, randomized, placebo-controlled trials have shown that there is substantial risk, with little or no benefit, associated with additional antibiotic treatment.  

Most patients presumed to have chronic Lyme are in category 1 or 2; antibiotic therapy in these patients is not warranted."

The IDSA has also given the following definitions to describe those who have Post-Lyme Disease Symptoms/Syndrome and those who have CLD:

"post-Lyme disease symptoms: fatigue, musculoskeletal pain, difficulties with concentration or short-term memory, or all of these symptoms when experienced by patients despite resolution of the objective manifestations of infection by Borrelia burgdorferi after antibiotic treatment. Seen in a minority of patients.

 post-Lyme disease syndrome: symptoms above lasting longer than six months. 

 chronic Lyme disease: The term has been applied to patients in a variety of contexts, including those with objective late manifestations (such as arthritis) and those with purely subjective complaints after antibiotic therapy. It is also applied to those with unexplained subjective symptoms without credible laboratory evidence for Borrelia burgdorferi infection irrespective of exposure to an endemic area. The term has also been applied to patients with other identifiable conditions such as multiple sclerosis."

So to make matters all the more confusing to the random passerby, the term "Chronic Lyme Disease" as currently used by the IDSA does not match the term "Chronic Lyme Disease" as it is used by the Lyme patient community.

The Lyme patient community, as you'll recall, states that CLD is caused by a persistent Borrelia infection. 

To further add to the confusion, the IDSA guidelines group used to define and use the term CLD the same way that Lyme patients currently do, and they still might in certain documents.

But now IDSA's current definition of CLD above is so broad as to be almost completely meaningless. It can be about objective late stage Lyme symptoms - but it is also stating that CLD is not related to Borrelia infection at all - especially if the patient lacks "credible laboratory evidence" for it (which is another issue - if that means serological testing, it is not always an accurate indicator for the presence of Lyme Disease - the most recent European study I posted bears this out) or perhaps it  isn't even Lyme Disease at all and it is MS.

This is unusually inconsistent with how one would determine definitions in many scientific realms. Consistency and specificity in language are important - especially in science. Words mean something.

Defining "Chronic Lyme Disease" in this manner, the IDSA might as well call it a dessert topping, floor wax, and a whole bass while they're at it.

My Diagnosis of Different Names

Today, for a more complete diagnosis, the IDSA would consider me a "Category 4 patient who has Post Lyme Disease Syndrome (PLDS)".

This would be based on case definitions, clinical diagnosis, and my patient history:

Several years ago I got bit by a tick and got a textbook case of Lyme Disease, and since then, I have not seen the same level of health I had before the bite and infection occurred. I suffer from fatigue, musculoskeletal pain, difficulties with memory and concentration, and a few other symptoms.

My original diagnosis for Lyme Disease was met on these points:

• I was bitten by a tick in an endemic area.
• I had an expanding erythema migrans (EM) rash around my tick bite.
• The rash continued to expand and within ten days I began to show full-blown signs of a flu-like illness matching symptoms of Lyme Disease.
• I have had positive serology for Lyme including a CDC positive Western Blot.

Anyway, I say all this to substantiate that in my case, that even by the IDSA's definition I have had Lyme Disease.

Not that this does me any good, to be believed by the IDSA on this point - identification under any of the above categories does nothing to help the Lyme patient receive effective treatment from IDSA doctors once the patient has received the standard treatment described in their guidelines.

Only LLMDs and alternative practitioners are trying to treat these groups at present.

What becomes an issue and is a big part of where the "Lyme controversy" comes from this:  

Whether or not the symptoms I had for weeks after treatment up through now are the result of continuing to be infected by Borrelia bacteria that are hard to kill off, or - by the current IDSA guidelines group's line of thinking - if some post-infectious process is taking place in my body which is producing my symptoms.

Once I went online seeking out information about Lyme Disease, it became clear that Lyme patient support groups and a number of doctors believed that Lyme Disease could be chronic in nature.

Other patients and some doctors have called my condition "Chronic Lyme Disease with coinfections".

And it was only later on that I began to dig more into research online to find out what different parties and institutions were finding and saying.

Most recently, Dr. Benjamin Luft spoke at an Institute of Medicine workshop in October 2010 and called my condition a sort of "Lyme Borrelia Complex". In so many cases, he knew ticks and patients were simultaneously infected with Borrelia and at least one coinfection, so this term may be more applicable than Lyme Disease to begin with.*

Documenting Chronic And Persistent Infection

While there is plenty of evidence that Borrelia spirochetes do persist in the host after antibiotic treatment - and even members of the IDSA have stated the spirochetes persist in their own research - the IDSA Lyme guidelines group currently question the spirochetes' ability to cause infection and has stated that they have no clinical significance. The IDSA has also stated that Lyme Disease is easy to treat and quick to cure.

For many Lyme patients, there is trouble with this stance because they have found research publications and patents by the same IDSA members which contradict their own position statements.

In the IDSA's and NIH's own research, Chronic Lyme Disease has been a consistently used term and their past usage of it has been connected with Borrelia infections which can persist in the host. As recently as 2005, IDSA members have filed a patent which mentions Lyme Disease as being difficult to eradicate. Also, researchers in other countries have found evidence that Borrelia infections can persist.

This leaves people questioning why it is they are finding contradictory statements about Lyme Disease coming from the same source - as well as from different ones.

Members of the IDSA guideline group have also stated that those with PLDS may be suffering from an autoimmune or immune dysregulation order. There has been no conclusive proof to date that CLD is caused by an autoimmune or immune dysregulation disorder, even though it may play a role in the disease process.  And unfortunately, unlike CLD, there is currently no treatment available for this disorder if it is the cause.

If I knew for sure this was the problem, and there was another treatment for it, I'd avoid taking one more milligram of antibiotics unless another infection came along - like bacterial pneumonia.

The Patient's Dilemma

So a patient in my position who is suffering from symptoms has these choices available to them:

1. Believe the IDSA and do nothing. Maybe it will get better over time.
2. Believe the IDSA and see a doctor or several doctors to find out if something else is wrong.
3. Don't believe the IDSA, and try longer antibiotic treatment. Maybe it will help.
4. Don't believe the IDSA, and try some alternative treatment. Maybe it will help.
5. Don't believe the IDSA, and try longer antibiotic treatment and something alternative. Maybe it will help.
6. Don't believe the IDSA and do nothing. Maybe it will get better over time.

It is not known how many CLD patients choose #1 or #6, and for how long that remains their position. Patients who have chosen #2 may start out with a non-CLD diagnosis and investigate whether or not they have CLD later on. The vast majority of CLD patients choose #3, #4, or #5 after they have been severely ill for some length of time and no other cause has been found.

Due to the severity of my symptoms that continued after the first three weeks of antibiotics, I made choice #3: continue antibiotic treatment. I tried additional treatment knowing what the risks were and went against the recommendations of the IDSA guidelines.

At the time, I was seeking to address what were not mild and vague symptoms but severe ones which prevented me from working and from even doing the most basic tasks like showering and preparing dinner.

I ended up visiting the ER more than a few times during my illness. If my condition were mild, I would not have been in the ER... I would have gone to work and made dinner.

In my case, extended antibiotic treatment eliminated a number of the symptoms I was experiencing - and for a time - diminished the intensity of my remaining symptoms. I did not think it was a poor choice to extend treatment, nor did my doctor. It was well thought out, and based on my responsiveness to treatment.

My issue now is that even as I have improved, I haven't regained my former health. Is this it,  have I hit the wall - or is there anything more I can do? I wish there was a definitive answer for me.

As it stands, I have the choice to either continue to follow treatment under an LLMD and/or alternative practitioner, self-treat holistically, or do nothing. I eliminate the other numbers in my spectrum of choices because I already see a primary care physician and other specialists concurrently to make sure I'm not missing anything else that could cause my symptoms as they come up. I have my bases covered.

What About The Original Question?

So we've gotten this far, and I guess I still haven't completely answered the question, "Is chronic Lyme real?"

What I've tried to do first in addressing that question is raise awareness that one's answer to that question depends on what they mean by the term, "Chronic Lyme Disease". The way the IDSA and its recent literature define CLD is the polar opposite of how the Lyme patient community defines CLD.

And I'm not entirely sure when the change in that use of the term took place and how consistently it has been applied - I still come across documents and research which use CLD in terms of persistent infection.

The IDSA needs to do more research on tickborne infections and clear up any inconsistencies in their research. It reflects poorly on them to contradict themselves, and to also base their guidelines on so few trials and limited understanding of not only Borrelia's pathogenesis but tickborne coinfections and immune factors as well.

Independent research groups and institutions with no investment or conflict of interests in tickborne disease research outcomes would be beneficial in providing unbiased confirmation of research that has been done - or better yet, do the research in areas the IDSA has been avoiding or under-serving.

I am not enamored of the one cause hypothesis when it comes to describing my own condition, because I don't think the issue is as simple as whether or not I have a chronic infection with Borrelia burgdorferi.

I may be infected with more than one strain of Borrelia and/or infected with a non-burgdorferi one.

There is objective evidence (serology) I have had at least one coinfection and it is one that has been proven to relapse. I may have other coinfections that have yet to test positive, and I may have additional coinfections for which there are no tests because they have not been identified.

It may be that coinfections are truly more my problem than Borrelia is.

I don't even think the issue is as simple as to whether or not I have an infection with Borrelia and Babesia, and possibly other coinfections, too. It's possible that I am a not only a polymicrobial soup du jour, but I am also suffering from an immune dysregulation disorder that was caused by the very pathogens which invaded me.

It's possible that my genetic profile left me more open to systemic disease than other people who have been bitten - but also possible that the specific genotypes of Borrelia are harder eradicate than others, that they have their own unique synergy with coinfections which make the infections harder to effectively treat, and that regardless of genetic background - would be difficult to treat in anyone.

And there are more possibilities which I am not listing here which may give rise to my condition.

So to say it's either persistent infection or an autoimmune/immune dysregulation disorder causing my problems seems a shortsighted simplification until more research is done and we really know what is going on.

After all of this discussion about whether or not chronic Lyme is real, the one thing to know is that the quote at the top of the page is definitely something to consider: the more you learn, the more there is yet to learn.

Any one post I make here - whether it's a study or commentary or article - is only going to touch on the edges of one facet of tickborne infections. The challenge is to take all of the information that is available and glean what is high quality, what is not, and what has yet to be determined to create a more informed picture of the problem.

Is Lyme Disease a disease that can be with you forever? Do certain conditions give rise to a lasting infection that can be eradicated eventually - and permanently? Is any symptom post-antibiotic treatment - even after much treatment - signs of a continuing infection or residual symptoms which will always be with you?

My suspicions are: conditionally yes, yes (but you could get re-infected), and maybe. More pieces of the picture are needed, and it will take separate posts just to begin addressing each of those questions on their own and confirm or even challenge my suspicions.

What does it take to confirm or challenge yours?

* I think that even in the Lyme patient community, many would think that CLD is a very basic definition of what they are suffering from and another term that I would use which may be more accurate based on their reported symptoms is this: Tickborne Disease Complex (TDC) or maybe even PTDC, where the 'P' stands for Persisting. Dr. Luft's term, "Lyme Borrelia Complex", isn't a bad idea, either.

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