Saturday, January 29, 2011

15 Resources: Alternative Treatment Links

Although I have an LLMD who is a bit old school (as I've said before), that doesn't mean that I don't endorse the use of any alternative treatment. Given my increasing intolerance to antibiotics, I may have to try more alternative treatment in the future, so this is something I am investigating.

I realize it's not a perfect world, and I wish everything was tested under double-blind random controlled studies, but I don't forsee that happening in the near future. If you're dealing with an illness now and want to try an alternative treatment, protect yourself by using treatments which have some research to back them, are not being sold as panaceas, and forewarn you of the potential for side effects, drug interactions, and risks. Avoid the overpriced and look for the most effective for the price, and start on a small dose if you don't know how it will affect you.

When at all possible, begin taking alternative medicine while under the care of a qualified and certified medical professional - either a regular physician who will regularly monitor your blood chemistry including liver function test and kidney panel, or a naturopath from a licensed degreed program such as Bastyr University in Washington State. (Note that there are only two universities in the US which have naturopathic graduate degrees and Bastyr has a rigorous curriculum.)

Three links I really find of use on alternative medicine:

Planet Thrive: Stephen Buhner on Lyme:
http://planetthrive.com/category/experts/buhner/


Stephen Buhner wrote the book, Healing Lyme, which besides having an herbal protocol for treating Lyme Disease also has a pretty good write-up on the lifecycle of Borrelia burgdorferi. For an herbal treatment book, it is amazingly well researched and does not do a hard sell; it comes with a list of benefits and potential side effects users may experience. The web site listed here is an extension of this, and Buhner has taken on individual patients' questions on his site. He does not see private clients and is paid nothing for this work.

The University of Maryland Medical Center Alternative Treatment Database: http://www.umm.edu/altmed/

Here is a link to one of the most comprehensive alternative medicine treatment databases online. Look up various treatment types (acupuncture, herbalism, aromatherapy, etc.), herbs, and supplements. Learn about different conditions and how herbs and supplements are used for treating them. Look up drug interactions, side effects, and warnings here - and ask a doctor and/or pharmacist for confirmation.

Bastyr University: http://www.bastyr.edu/

Bastyr University in Washington State is a non-profit, private university offering both graduate and undergraduate degrees, with a multidisciplinary curriculum in science-based natural medicine. The University is recognized globally for its curriculum and research.

Disclaimers: I don't assume that everything at these sites is correct. I am not responsible for content. I endorse these sites as an improvement over many other alternative sites that have been available due to their own disclosures on side effects, detailed reports, and the use of citations.
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2 Commentary: Finding the right treatment that works

I'm realizing that it is taking longer than I thought it would to put together posts on persistence - if you read the chain of comments on this TED talk on quorum sensing, I had an interesting exchange with someone anonymous (anonx) which got me thinking of how to write about how Borrelia persists in the host (I recommend checking it out; it's worth it).

There's a lot of ground to cover, and it may take a while for me to firm up an outline or structure for the posts, which is what I'm working on bit by bit. In the meantime, other topics are a bit easier to write about because they are editorial in nature and not so dependent on citations.

I decided I should explain some of the thinking behind this cryptic post a couple days ago, because some people might have wondered what I was talking about and one person marked "???".

So, I'm going to take each of those two statements in that cryptic post and write more about them, starting with the first:


Just because someone is right about something, doesn't mean they are right about everything.


Some time ago I posted something I received in email about including the middle. This had nothing to do with what I'd posted about Pamela Weintraub's statement, to be clear on it, but it made some valid points.

In "Including the Middle",  I like to cite this excerpt:
"That there is no One True Way does not mean that all ways are equally valid, or that there are no false ways.  Similarly, there may be no one thing that works for everyone, but it does not follow that therefore, everything works for someone.  There are things that don’t work for anyone."
And I think this is true of treatments for Lyme and coinfections.

I've noticed there's a tendency for some people to think that if some part of a doctor's treatment or protocol has helped them regain their health or show progress that they assume that the rest of their treatments or protocols are likely to help to or have a well-reasoned basis behind them.

I can see where I'd want to hope that this is the case, but in my experience, this hasn't necessarily been the case. 

I'd have to say that two of the biggest frustrations I've experienced being a Lyme/coinfection patient have been:

1) Being treated dismissively by certain people - especially medical professionals who do not understand or validate the existence of my condition - and 

2) How hard it is to figure out what the best way is to treat my condition and what the truth is about it.

There is a ton of information out there to weigh and consider. It gets to the point of information overload for me, and I suspect that this is the case for many other patients trying to regain their health. Because of this, I think the fallback position is simply to trust one's LLMD to make treatment decisions.

It's not the worst approach I can think of in many cases. I might be biased because I think my LLMD is pretty good, and makes sound treatment decisions based on the research available out there. 

Even though I mostly trust his treatment approach, because I am who I am, I do ply him with questions now and then. Sometimes I have to stop my current treatment and try a different approach. Then we work together to find that next step.

But that isn't the full story for treatment across the board for everyone in every situation. In general, there is so much that remains a huge unknown about Lyme and coinfections that a lot of treatment plans practitioners come up with (both allopathic and alternative) are purely experimental. 

This is not to say they are all wrong. But it's to say that we have no clear way of knowing what really works for which group of patients, and the repeated mantra I have seen in the Lyme patient community has been that everyone is an individual when it comes to treatment.

As it stands, individual research is often the approach du jour, and there is no one guiding the process. Outside of consulting an LLMD, everyone comes up with their own method of deciding what they are willing to try and not try, do and not do. And this wouldn't be so bad if it weren't for the fact that people make decisions which are not informed, not well-researched, and can lead to Things That End Badly.

How does one go about changing this state of affairs?

Is it a worthwhile pursuit to try changing it?

I suspect that if one were to begin seriously tracking the data on certain groups of patients, that a pattern would be found as to which treatments are more effective for certain cases and that could be measured and quantified. We might also find which ones have been harmful for certain patient groups.

Right now, I don't see so much of this work going on and it would be to the patient community's great advantage if all the LLMDs began to collectively pool this data and share it (while protecting patient privacy, of course) with us. Then we'd know what is working and what is not - or at least get an idea of it. 

If a bigger number of patients try the protocols that are known to work better over time, then more successes can be documented within the community and also for institutions outside of it. This could only be an asset for everyone.

I'd also like to know what isn't working for patients on the whole - neither showing improvement nor cure - and dump it.  It is just as important to report side effects and treatment failures as it is to report benefits and success.

Of course, this is difficult to test when someone has a condition which waxes and wanes and has cycles, isn't it? 

I could be getting better because my Borrelia has gone into a dormant state, or I've just finished having a Herxheimer reaction and now that that's over I'm beginning to feel better. Or I changed antibiotics recently, and that helped my symptoms to improve. What is the true cause of my improvement? Do I care why, or do I only care that it happened?

Well, I do care that it happened. I want out of hell, that's to be expected. But caring why it happened is more useful in the long run because then I know I'm on the right track and doing something that works. I just need to prove it, and it would be good to see other people with my condition and medical profile reproduce my results. Then we know we might be on to something.

I'd like to see treatments based on something that is quantifiable and measurable across the board where we can see there are results, and not just have it be hearsay that a few patients got better by trying x or y protocol or herb on their own or under Dr. Foo's care or whatever one wants to fill in the blank there. Otherwise I could just be throwing money at something that is absolutely useless - or worse, taking something that isn't good for me. 

Even better would be to find someone who is totally independent and conflict-of-interest-free to be able to repeat and confirm treatment data using the same patients as well as new ones. Someone not involved with IDSA, ILADS, or any other group which potentially has a stake in the outcome. Because then from the outside, once the Lyme community's suspicions are confirmed and already existing data about tickborne infections are proven by someone independent of all the issues involved, then more credibility is achieved.

Given that those within the community are the most invested in the outcome of any study, the best source of credibility would come from any group which had proof of the problems that dog us who are neutral about the outcome. 

Perhaps after they did their research and got the results, they would be anything but neutral. One could hope...

I'd also like to see more energy put into the drive for requesting and requiring proof that something works, and questioning the use of something novel and newly marketed (whether by a supplement company, another patient, or a doctor of any stripe) for its effectiveness and safety.

It would be refreshing to see more people openly questioning in general, because otherwise how do I know what their individual process is in deciding how they made a treatment choice one way or the other without asking questions? Both for and against? Knowing about their process would help me and other patients to make informed decisions.

Right now, I'm still tripping over seeing someone claim on a given support group that Lyme Borrelia cysts last forever and can survive fires, and a sad number of patients worrying they will never get cured because of this statement. 

To them I have to say this: 

If you don't like what you are hearing, ask yourself these questions first: 

1) Is what I'm hearing true?

2) How can I find out if it's true? 

Then work on figuring out what a reliable source is for those answers. 

I make you any bet the source is not the person making the original statement or claim. Look elsewhere.

(In this case, you might want to begin with remembering what I wrote about Syphilis and Malaria, and look up the viability and temperatures at which Borrelia dies.)

Conversely, I think that if something sounds too good to be true, that if you like what you're hearing, if it raises your spirits and gives you more hope than you've ever had before... Then ask yourself those same two questions and figure out what a reliable source is for those answers.

Otherwise, you could be chasing down something that isn't worth your time, money, effort, and most of all: your health.


* Note: "He's" and "his" are being used as general pronouns here, as I get tired of writing "S/he's" and "his/her" all the time and think it is harder for people to follow the flow of writing with those in it. Apologies to the feminists reading along who prefer me to use "she" and "her" instead. I advocate English coming up with a gender neutral pronoun like other languages have.

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Friday, January 28, 2011

0 Video Parody: Bad Project

I'm working on posts about the persistence issue in Lyme Disease. In the meantime, I came across this video parody of Lady Gaga's "Bad Romance" that I thought was kinda funny.

This is dedicated to all of you overworked graduate and doctoral researchers working in bio and microbio school labs...


I think the biohazard bag dress on their version of Lady Gaga is a real trip... And oh, they sing about Western blots, too!

Warnings: Use of the word "bitch" NSFW.  You may want to use headphones...
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Tuesday, January 25, 2011

0 A few words on being right and alliances

I'll be posting more later, but for now here are two thoughts to chew on:

1) Just because someone is right about something, doesn't mean they are right about everything.

2) The enemy of my enemy is my friend... unless that enemy is my enemy as well.

For those of you whom are active participants in the Lyme patient community, consider reflecting on those thoughts in line with recent events.

For those of you whom are not such participants, these thoughts have value independently.
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Sunday, January 23, 2011

0 Administrivia: New page and updates

Just a brief note for those revisiting or who are new to my site:

1) I've added a new page about the middle ground which contains transcribed notes on Pamela Weintraub during the October 2010 IOM  Q & A session. That page is: The Middle

2) I've updated the FAQ, too.

That is all.
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Friday, January 21, 2011

17 Video: How bacteria "talk" and how to make them shut up

Another interesting TED talk today.

This one is by Bonnie Bassler, who discovered how cell populations use chemical powwows to stage attacks, evade immune systems and forge slimy defenses called biofilms. For that, she won a MacArthur "genius" grant.

At the beginning of Bassler's slideshow, she displays Lyme Disease as one of the bacteria we are in a war against, and she proceeds to explain how bacteria communicate with one another to invade us.

Once bacteria reach a certain population level after dividing, they release a chemical message that triggers their virulence. This communication is known as "quorum sensing" and many bacteria do it.

There is also another bacterial communication method known as "efficiency sensing" which is not mentioned here, but worth investigating.

I highly recommend taking 18 minutes out of your day to watch this video, and think about the implications of her research for Lyme Disease patients - as well as for anyone needing to treat bacterial infections in the future.



Additional Resources:
Bonnie Bassler's Homepage: http://www.molbio.princeton.edu/index.php?option=content&task=view&id=27
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Thursday, January 20, 2011

0 With Apologies To Maslow




This about covers it for me... other than I think I'd substitute "To bitch" for "To complain", and "Coffee" for "A rare sweet".  How about you?
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Wednesday, January 19, 2011

2 Polymicrobial Infections

I know that in my comment on my last topical post, “Syphilis and Vaccines”,  I wrote about how I thought it was scary that infecting patients with Malaria in order to raise a fever to kill Syphilis because 10% of patients subjected to the procedure died. This was considered an acceptable risk at the time, since there was no cure for Syphilis and once it moved to the third stage, madness and death weren’t far behind.

In this day and age, Syphilis and Lyme Disease are both treated using antibiotics, and the thought of a Lyme patient adding one more infection to their bodies willingly makes me shudder. For the current LLMD maxum commonly is, “Treat the coinfections first, then work on the Lyme Disease”. The thought being that the immune system is too busy responding to the coinfection or coinfections to really begin fighting off the Lyme Disease, which is a more entrenched organism.

And I’ve wondered, is there any data to back this statement up? Surely someone must have done research, but it is not something an LLMD has sat down and explained to me in great detail.

In my entry, “Syphilis and Vaccines”, I discussed a number of attributes of Syphilis infections and Treponema pallidum. One thing I mentioned was that those who suffered from both Syphilis and HIV were more likely to have severe disease.

It is already fairly well documented that coinfections or polymicrobial infections do have an unusual effect on the immune system and often increase the severity of patient disease. Often, but not always.

Take a look at this graph as a short tutorial on the effect of concurrent infection with bacterial and fungal infections. The graph makes a point of how having both infections can contribute to patient outcome, emphasis mine:

"Given the complexity of the interactions that can occur in a polymicrobial infection, including those between the pathogens and between the pathogens and the host, it is useful to define the principles of survival-curve interpretation that can be applied to any model of a polymicrobial infection (see the figure).

If the host killing by a polymicrobial infection is equivalent to the sum of killing by infection with each pathogen alone (represented by the red and blue lines in the graph), then the killing can be termed 'additive' (represented by the solid black line in the graph).

This suggests that the virulence of the two pathogens together is greater than that of either alone, but it may not be due to pathogen–pathogen interactions or changes in host–pathogen interactions; the two pathogens could be killing through independent mechanisms acting over a similar time course.

If the host killing by a polymicrobial infection is greater than the sum of killing by infection with each pathogen alone, then the killing can be termed 'synergistic' (represented by the area below the black line in the graph). This implies that the virulence of the two pathogens is not only greater than that of either alone but also greater than that which would be expected if they were killing by independent mechanisms over a similar time course.

This pattern suggests a synergistic pathogen–pathogen interaction or a change in host–pathogen interactions that is characterized by increased host susceptibility to one or both of the pathogens. 

Interpretation becomes challenging when the host killing by a polymicrobial infection is less than additive killing (represented by the area above the black line in the graph).

This pattern could have several explanations:
  • that there is an antagonistic interaction between the pathogens, whereby the virulence of one organism is reduced by the other; 
  • that the host response to the combined infection is greater or more efficient than the response to infection with either pathogen alone; 
  • that the two pathogens mediate killing or virulence through the same pathway, which becomes saturated; or
  • that one pathogen kills more rapidly than the other, preventing the slower pathogen from having any impact on host killing. 
These simplistic concepts should serve well for the future interpretation of survival curves for polymicrobial infections. Moreover, they highlight the importance of assessing and reporting the virulence end point for the pathogens alone and in combination." [1]

Although bacteria and fungal coinfection or polymicrobial infection is outlined here, the same basic principles may be applied to bacterial-bacterial or bacterial-protozoan infection as well.

Are polymicrobial infections - simultaneous infection with more than one pathogen - always going to have a more serious effect on people? 

Not always, as some bacteria have a beneficial effect or neutral effect in a given organism. Consider how your body has many different bacteria that play a positive role, such as bacteria in your intestines that help break down food, produce vitamins, and support immunity. C. difficile, feared amongst those taking antibiotics, is often already living in us without causing any problem at all - it is only once it dominates the balance that it is problematic.

But there are many cases where polymicrobial infections are not a good thing - or even neutral thing - at all.

A search of PubMed and Oxford Journals on polymicrobial infections turns up a lot of data on MRSA polymicrobial infections (mostly soft tissue infections; some ventilator-based), infections involving the diabetic foot, immune-suppressed cancer patients, sepsis, and peritonitis.

Only a small fraction of all polymicrobial infection research is focused on the pathogens which concern tick-bitten patients; most of it is about serious acute infectious states that regularly dog hospital staff and surgeons.

That which has been published so far on polymicrobial tick-based infection has produced conflicting results. But there are some broad points to be made before drilling down, and there are things to consider even in just scratching the surface of this phenomenon. (My point in writing here today is to scratch the surface and introduce these ideas, anyway.)

So how common is a polymicrobial infection from a tick bite, anyway?

More studies are needed, but this should shed some light on a highly endemic region.

First of all, there is polymicrobialism with Borrelia alone.

Ticks can carry more than one genotype or strain of Borrelia simultaneously, with each strain having its own clinical significance and symptom presentation.

Dr. Ben Luft and a group of other researchers analyzed ticks collected from across four US states and in Southwestern Germany. In their analysis of American Ixodes ticks, of the 169 B. burgdorferi-positive adult I. scapularis ticks characterized, 62% (n=104) had a single genotype, 34% (n=57) contained two genotypes and 5% (n=8) had three or more genotypes of Borrelia.[2]

So just looking at Borrelia alone, we have may have nearly 40% of ticks with polymicrobialism. Then one can also consider adding other pathogens to the list...

Published in 2010,  Assessment of polymicrobial infections in ticks in New York state, contained this gem:
“A single tick bite can lead to a polymicrobial infection. We determined the prevalence of polymicrobial infection with Borrelia burgdorferi, Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and Powassan virus in 286 adult ticks from the two counties in New York State where Lyme disease is endemic, utilizing a MassTag multiplex polymerase chain reaction assay. Seventy-one percent of the ticks harbored at least one organism; 30% had a polymicrobial infection. Infections with three microbes were detected in 5% of the ticks. One tick was infected with four organisms. Our results show that coinfection is a frequent occurrence in ticks in the two counties surveyed.” [3]
If 71% of 286 ticks were infected at all, I’d be making sure I’m dressed to the nines in permethrin soaked camos in those counties. That is pretty nasty endemic for Lyme Disease, right there. But it doesn’t stop there - 30% of those ticks were infected with more than one organism simultaneously. This at least gives us an idea how common polymicrobial infections are in ticks in part of New York.

If one of those ticks in that 30% has bit you - or your lottery draw is so awful you received four different pathogens at once - not including more than one kind of Borrelia - what are you going to do? 

Scream at first, probably.

What studies are available that show the impact of more than one tickborne infection on people?

Most of what we have are murine (mouse or related rodent) studies. This is a fairly common procedure, as mice are thought to replicate a lot of the same processes that occur in humans. So far, the data is mixed - but this may be due to study method and design as much as it is by polymicrobialism.

In the 2005 study, Babesia microti and Borrelia burgdorferi Follow Independent Courses of Infection in Mice, mice were simultaneously infected with Borrelia burgdorferi and Babesia microti and monitored for 21 days, then killed. Poor mice. Their organs were then examined and samples were taken. In this study, researchers compared the effect of coinfection on disease severity, by measuring the percentage of infected red blood cells (RBCs) and degree of splenomegaly (Babesiosis) and by spirochete dissemination, carditis, and arthritis (Lyme Disease), in mouse models simulating risk factors for human disease.

The result of this study was that “Babesiosis followed its normal course of infection in coinfected mice, without evidence for increased severity, as reflected by percentage of parasitemia, spleen weights, and hematologic and clinical chemistry parameters. Likewise, Lyme Disease followed its established course and severity in coinfected mice, as reflected by the degrees of spirochete dissemination and arthritis.” [4]

In other words, unlike the black line on the chart we saw earlier on, coinfection with both Babesiosis and Lyme Disease was not synergistic, and severity of each disease was the same as it would be if the patient would have been infected with each pathogen individually and independently. 

But this is just one study from 2005 with a specific design that may or may not prove what polymicrobial infection with these agents means for the patient.

In fact, this specific study was criticized later by reviewers for two design flaws: 1) the Babesia microti strain used was adapted to lab mice and may have been made less virulent than strains of Babesia which had been used in previous experiments demonstrating how coinfections increase disease severity, and 2) it lacked more concrete markers to determine disease severity such as cytokine levels and symptoms of arthritis in their mice.

The shortcomings I see in this study are that it doesn't map changes in cyotkine levels over time nor does it capture the effects of long-term infection on subjects. If the infected mice are put down for autopsy after only 21 days of infection, does this truly give an idea of how disease has affected them?

I am already not pleased that animal research and testing is still a required part of science as it is, and the thought of placing animals in a position where they suffer more isn't pleasing to me any more than it is for the next person. But I do think there is a correlation between the severity of a disease and its duration that cannot go unobserved, and somehow there must be a means to test it.

Certain studies need to be made where one is not just looking at peak infection levels of Babesia in the blood or acute infection, but the effect of long-term coinfection on the immune system with subclinical through moderate levels of infection. This is more likely to be the case in humans who are underdiagnosed or misdiagnosed, who may not get a rash from the specific Borrelia bacteria infecting them and may not show evidence of Babesia infections either through blood smears or early and acute symptom presentation.

In an earlier study, Concurrent Lyme Disease and Babesiosis: evidence for increased severity and duration of illness, fatigue was notably increased in coinfected patients, and there was an increased array of symptoms of longer duration in the subjects. However, even with greater detection of Borrelia burgdorferi DNA in the blood, arthritic, cardiac, and neurologic symptoms were actually similar to control (uninfected) groups [5]. And in yet another study there was no association between B. microti and B. burgdorferi coinfection and increased Lyme Disease severity.[6]

Looking at another earlier study, Increased Arthritis Severity in Mice Coinfected with Borrelia burgdorferi and Babesia microti, the authors stated, "As observed in previous studies, BALB/c mice infected with B. burgdorferi alone developed mild arthritis at 15 and 30 days, reaching maximum (albeit low) arthritis severity scores 15 days after inoculation. In contrast, the severity of arthritis was significantly increased for the coinfected BALB/c group at day 30."[7] So in this study, arthritis severity was significantly worse in coinfected mice than those infected with Borrelia burgdorferi alone.

Interestingly, the authors made this statement, too: "Recent studies of B. burgdorferi and Anaplasma coinfection suggest an immunologic interaction that ultimately enhances pathogenicity of B. burgdorferi [8]. These effects may have a significant impact on the persistence of B. burgdorferi and the immunologic selective pressure it is subjected to. We did not observe an increase in B. microti parasitemia as a function of coinfection, but B. burgdorferi infection might conversely affect immune responses to B. microti."

In other words, it is Borrelia burgdorferi which affected the immune system's response to Babesia microti, and not the coinfection affecting the Borrelia burgdorferi as it had been predicted.

In the 2002 study, Disease-Specific Diagnosis of Coinfecting Tickborne Zoonoses: Babesiosis, Human Granulocytic Ehrlichiosis, and Lyme Disease, the authors state that,"Because these diverse Ixodes-transmitted infections frequently are cotransmitted, the spectrum of acute disease may be highly variable. Previous descriptions of the clinical manifestations of these diseases were recorded before the likelihood of coinfection was widely recognized and before many current diagnostic tests became available. Only 2 such systematic analyses of the clinical course of acute infection with 2 of these agents in North America are now available. [5, 9]

In this data-rich survey, of the 192 patients from New England (CT, MA, RI) surveyed:
  • Most patients with Lyme Disease, either alone or in combination with Babesiosis or HGE, presented both with an erythema migrans rash and flulike symptoms.
  • A higher percentage of patients with concurrent Lyme Disease and Babesiosis or HGE experienced flulike symptoms than did those with Lyme disease alone.
  • An erythema migrans rash by itself is more suggestive of Lyme Disease alone than it is of Lyme Disease with a concurrent disease, whereas flulike symptoms without an erythema migrans rash are more suggestive of Lyme Disease with a concurrent disease than of Lyme Disease alone.
  • The combination of fever, chills, and headache was noted in approximately one-half of the patients with Lyme Disease coinfection (32 [44%]), compared with approximately one-tenth (12 [13%]) of those with Lyme Disease alone.
  • Patients with Lyme Disease alone reported fewer and more-transient symptoms than did those infected with the agents of Babesiosis or HGE or those with Lyme Disease and concurrent Babesiosis or HGE.
In summary, the combination of fever, chills, and headache in patients with Lyme Disease suggests that these patients are concurrently infected with the agents of Babesiosis, HGE, or both. Concurrent infection tends to increase the diversity and duration of symptoms attributed to Lyme disease.

Early Symptom Profile of 192 Surveyed Patients

In terms of dissemination of the disease in patients:
"Spirochetal dissemination into skin, as assessed by the development of disseminated erythema migrans rash, was observed in 13 (15%) of the patients with Lyme disease alone and in 13 (18%) of the patients with Lyme Disease and concurrent babesial or ehrlichial infection. Joints became swollen in 8 (9%) of the patients with Lyme disease alone and 6 (8%) of the patients with Lyme Disease and concurrent infection. Only 1 patient (1%) with Lyme disease alone received a physician's diagnosis of arthritis, compared with none of the patients who had Lyme Disease and concurrent infection. A physician's diagnosis of acute neurologic abnormalities (e.g., Bells palsy or meningitis) was made for 2 (2%) of the subjects with Lyme Disease alone and 2 (3%) of those with Lyme disease and concurrent infection. None of our patients had acute cardiac complications diagnosed. In sum, concurrent Babesiosis or HGE does not appear to increase the probability of acute dissemination of the Lyme Disease spirochete into blood, skin, joint, nerve, or heart tissue."
In other words, those patients surveyed did not demonstrate earlier acute dissemination rates due to coinfection compared to patients infected with a single organism.

Arguably, one of the supporting arguments for longer term treatment of Borrelia infection would be to show that coinfection with other tick-borne pathogens could increase the severity and persistence of Borrelia burgdorferi infection due to limited immune response. But we have a ways to go yet, and more research is needed to understand the individual mechanisms and processes of tickborne infections independently - let alone as a group.

So knowing all this now, what is the patient's best choice? Treat the coinfection first, then treat the Lyme Disease, as has been said by LLMDs all along?

Logic seems to dictate that one treats first and foremost the disease that is giving one the greatest number of symptoms and is of the greatest severity. Treating an acute infection requires immediate attention, as the symptoms of acute Babesiosis can be serious and lead to complications - and in a small percentage of cases, it is fatal when acute. Treating a subclinical case or mild case requires a different approach, and while literature supports letting a subclinical case of Babesiosis resolve on its own, if the immune system is already beating down a polymicrobial infection, it might not resolve so easily.

The bottom line seems to be thus far that if you have more severe flulike illness after a tick bite, look for coinfections - especially Babesia. But know that odds are good that you have Lyme Disease, too. Treat them both.

Disclaimer: I am not a doctor, nor do I play one on television. The preceding is not to be used for medical advice and is only informational.

References:
[1] Anton Y. Peleg, Deborah A. Hogan, Eleftherios Mylonakis. Medically important bacterial–fungal interactions. Nature Reviews Microbiology 8, 340-349.
[2] Chris D. Crowder, Heather E. Matthews, Steven Schutzer, Megan A. Rounds, Benjamin J. Luft, Oliver Nolte, Scott R. Campbell, Curtis A. Phillipson, Feng Li, Ranga Sampath, David J. Ecker, and Mark W. Eshoo Genotypic Variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe. PLoS One. 2010;  5(5): e10650.
[3] Tokarz R, Jain K, Bennett A, Briese T, Lipkin WI. Assessment of polymicrobial infections in ticks in New York state. Vector Borne Zoonotic Dis. 2010 Apr 10 (3):217-21.
Infect Immun. 2005 Sep;73 (9):6055-63.
[4] James L. Coleman, Dreania LeVine, Charles Thill, Christopher Kuhlow, and Jorge L. Benach Babesia microti and Borrelia burgdorferi Follow Independent Courses of Infection in Mice. J Infect Dis. 2005 192(9): 1634-1641.
[5] Krause PJ, Telford SR 3rd, Spielman A, et al. Concurrent Lyme disease and babesiosis: evidence for increased severity and duration of illness. JAMA 275:1657-60.
[6]  Wang TJ, Liang MH, Sangha O, et al. Coexposure to Borrelia burgdorferi and Babesia microti does not worsen the long‐term outcome of Lyme disease. Clin Infect Dis 31:1149-54.
[7]  Increased Arthritis Severity in Mice Coinfected with Borrelia burgdorferi and Babesia microti.
[8] Thomas V, Anguita J, Barthold SW, Fikrig E. Coinfection with Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis alters murine immune responses, pathogen burden and severity of Lyme arthritis. Infect Immun 2001; 69:3359-71.
[9] Belongia EA, Reed KD, Mitchell PD, et al. Clinical and epidemiological features of early Lyme disease and human granulocytic ehrlichiosis in Wisconsin. Clin Infect Dis 1999; 29:1472-7.

Additional Resources:
Interesting article on using mice for research, “The Rodent Revolution”: http://f1000scientist.com/article/display/16597/

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Tuesday, January 18, 2011

0 Salon article: How to tame the media, not be tamed by it

I don't usually refer to Salon here that much and read them only on occasion, but I thought this article provided food for thought and thought you might also enjoy comments on it:

How to tame the media, not be tamed by it

It's about looking at what you read with a critical eye, and questioning everything you read.

One funny thing about the article is that by the end of it, the audience is questioning the very article which recommended they question what they read.

Brilliant.
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Sunday, January 16, 2011

2 Hello European Readers: a query

I noticed a lot of my hits are coming from the Netherlands and Germany... Welcome to Camp Other!

Is er een Borrelia-gerelateerd onderzoek in het Nederlands geschreven ik zou moeten weten?

Gibt es gute Borrelien-Forschung in Deutschland sollte ich wissen?

I can get through original documents written in either German or Dutch with some help, if they aren't already translated into English - but prefer a good English translation copy if given one.

Dank u! Danke! Thanks!
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Friday, January 14, 2011

3 Syphilis and Vaccines

Let's learn a few things about Syphilis and the bacteria which causes it, Treponema pallidum

The reasons why I am looking at Syphilis on a tickborne-related illness blog are because a) it is spirochetal, b)  there is speculation on the similarities between Syphilis and Lyme Disease, c) some of the data on Syphilis may be informative in how one thinks about other infections or infection states, and last but not least d) some of the information given in this post provides background information for future posts.

So, what do we know about Syphilis? Nasty thing to get. I know I wouldn't want it. But then, I have Borrelia in me and that's bad enough; it's not even quite sure which Borrelia genotypes I'm hosting because tests I've had don't tell me.

Perhaps in the future, Dr. Ben Luft will develop a more accurate test, but I digress...

The overview

Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum subspecies pallidum. The primary route of transmission of syphilis is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis.

The signs and symptoms of syphilis vary depending on which of the four stages it presents in (primary, secondary, latent, and tertiary). The primary stage typically presents with a single chancre; secondary syphilis with a diffuse rash; latent with little to no symptoms; and tertiary with gummas, neurological, or cardiac symptoms. 

Blood tests are commonly used to diagnose syphilis; however those tests produce false negatives in 20-30 percent of primary syphilis cases, allowing for the possibility of ongoing transmission.[1]

Unfortunately, one of the reasons for inaccuracy in early detection of Syphilis is infectious disease specialist lack of access to darkfield microscopy. According to study author Deborah Dowell, MD, of the Centers for Disease Control and Prevention (CDC), "Eighty-one percent of our survey respondents did not have access to darkfield microscopy. These clinicians should treat presumptively if they suspect early syphilis in their patients." Dr. Dowell also notes that there is a clinical and public health need for a rapid point of care test to reliably diagnose primary syphilis.[1]

Right now, testing is a two-tier procedure:


Only if an EIA test is positive does the patient receive an RPR or VDRL test that is confirmatory, though it is a non-treponemal test that confirms the original reactivity. If the initial EIA test is negative, then the patient is considered to be uninfected with Syphilis. This is a serious problem due to the number of false negatives in the primary stage of infection.

The infection can be effectively treated with antibiotics in its earlier stages, specifically intramuscular penicillin G. There is also experimentation using oral azithromycin for treatment, though some strains are shown to be macrolide resistant.

Syphilis is believed to have infected 12 million people worldwide in 1999 with greater than 90% of cases in the developing world. Rates of infection have increased during the 2000s in many countries, including the United States.

The majority of cases have been concentrated in large cities, such as San Francisco, Baltimore, Miami, Washington, DC, and New York City, and scattered throughout the South. The highest numbers are found among inmates in correctional facilities, among men who have sex with men, and those co-infected with HIV.[2,3]

Syphilis infection increases the risk of transmitting and acquiring HIV infection. Not only are syphilis lesions a portal of entry for HIV but the immune cells that carry and are successful to the virus, macrophages and T lymphocytes, are found in abundance in syphilis lesions. There is also some experimental evidence for direct involvement of T. pallidum in facilitating HIV infection and progression.

Treponema pallidum

Treponema pallidum is a species of spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis, bejel, pinta and yaws. It is not seen on a Gram stained smear because the organism is too thin.

What can we learn about it?

Electron micrograph of T. pallidum
Morphology 
  • It is small, about 0.2 µm in diameter and between 6-15 µm in length. A human hair, in contrast is 40-50 µm.
  • To get an idea of how small this really is, check out The Scale of the Universe and place the slider between the human body icon and the atom icon. Check out the red blood cell. Yeah, you're getting warm... that's how small it is.
  • It requires dark field microscopy to see it. 
  • It has regular, tight spirals and displays rotary, flexive and to-and-fro movements.
  •  It has a cytoplasmic membrane enclosed by an outer membrane. 
  • A thin layer of peptidoglycan is sandwiched between these membranes to give added stability.
  •  The periplasmic space contains endoflagella that facilitate the characteristic motility.

Small genome
The genome of T. pallidum is much smaller (1.14 Mb) than that of many conventional Gramm-negative bacteria, for example, E. coli (4.6 Mb) and B. subtilis

Infectivity
  • T. pallidum is transmitted by direct contact, usually sexual. 
  • Infection is initiated when T. pallidum penetrates dermal microabrasions (small cuts) or intact mucous membranes (e.g. oral, ocular, nasal, vaginal). 
  • Studies have shown that 16 to 30% of individuals who have had sexual contact with a syphilis-infected person become infected. Actual transmission rates can be higher. The 50% infectious dose is estimated to be only 57 organisms. 
  • Upon initial infection the parasites prefer to multiply at the point of entry causing the inflammatory response and formation of characteristic chancre (an open sore).
  • From the chancre the treponemes disseminate rapidly to the blood and lymphatics and make their way to different parts of the body including Central Nervous System (CNS). 
  • T. pallidum has been shown to induce the production of matrix metalloproteinase-1 (MMP-1) in dermal cells. MMP-1 is involved in breaking down collagen, which may help T. pallidum to traverse the junctions between endothelial cells and penetrate tissues.
  • The only known natural host of the bacterium is the human. Combined with transmission mode, this fact gives hope to a possibility of complete eradication of the syphilis in a future.
Challenges for research
  • Treponema pallidum cannot be cultivated long term (more than 100-fold ~7 generations) in vitro. 
  • In laboratory, T. pallidum can be only maintained by propagation in rabbits. 
  • Because of fragility of its outer membrane, researchers are unable to modify the bacterium genetically in order to conduct experiments, which in many other bacteria clarified various aspects of their biology such as protein functions, mechanisms of virulence, and others.
The detailed nitty-gritty about Treponema pallidum

Metabolic deficiencies
  • The bacterium lacks tricarboxic acid cycle enzymes and the electron transport chain. 
  • T. pallidum depends upon glycolysis as the sole pathway for the synthesis ATP. 
  • In addition, a pathway for amino acids and fatty acids synthesis as well as for metabolism of alternative carbon energy sources and for the synthesis of nucleotides and enzyme cofactors seems to be absent. 
  • These traits suggest that the bacterium derives most essential macromolecules from its host (enzymes for interconversion of amino acids and fatty acids as well as homologs of transporters for a variety of amino acids are present). 
  • Because the T. pallidum genome encodes no known homologs to porin proteins, it is unclear how nutrients are moved across the outer membrane into periplasmic space.
Slow multiplication rate
T. pallidum divides very slowly, doubling every 30-33 hours in vivo. In contrast, Nesseria gonorrhoeae divides approximately every 60 minutes, and E. coli every 20 min.

Limited stress response and heat tolerance
  • The lack of enzymes that detoxify reactive oxigen species such as catalase and oxidase makes T. pallidum vulnerable to oxygen. 
  • In a number of reports best survival occurred at low concentrations of oxygen (1-5%). 
  • At least one of its enzymes is unstable at normal body temperature. 
Heat therapy for late neurosyphilis was introduced in 1918 by the Viennese psychiatrist Julius Wagner von Jauregg, a discovery for which he later won the Nobel Prize in Medicine. He inoculated patients with malaria pathogen and 10 to 12 febrile episodes later, treated them with quinine. 

The high temperatures induced by this regimen, along with other methods of raising body temperature, presumably killed T. pallidum in the CNS. Doctors reported high percentage of complete or partial remission of general paresis symptoms (although the treatment killed about 10% of patients - don't try IHT at home, kids!).

For a long time researchers tried to explain mechanisms underlying the natural course of the syphilis: recurring clinical manifestations separated by prolonged asymptomatic periods. In early 1970s it was believed that treponemes cause specific or generalized immunosuppression and are resistant to phagocytosis by macrophages and neutrophils. 

Later studies showed, however, that initial immune response of host to treponemal assault, though slow to develop, is rather robust, and as treponemes reach peak numbers, macrophages begin to infiltrate the lesions resulting in rapid clearance of overwhelming majority of the parasites from the tissue. However, some portion of the treponemes remains untouched and continues living in the host causing a persistent infection.

Lack of endo- and exotoxins
  • The T. pallidum lacks liposaccharide (LPS), the endotoxin found in the outer membranes of many gram-negative bacteria. 
  • The attachment of T. pallidum to cells does not harm the cells (no swelling or indentation). 
  • The cultured cells survive for 5-7 days with actively motile attached treponemes in quantities up to 100 organisms per cell and remain viable. 
  • This indicates that cytolytic enzymes or other cytotoxins most probably do not play a role in syphilis pathogenesis.
Invasion of "immune-privileged" tissues
T. pallidum penetrates a broad variety of tissues, including so-called "immune privileged": the central nervous system, eye, and placenta, where there is less surveillance by the host's innate immune system.

Ability to maintain infection with few organisms
T. pallidum may also exploit its slow metabolism to survive in tissues, even those that are not immune privileged. By maintaining infection with very few organisms in anatomical sites distant from one another, T. pallidum may prevent its clearance by failing to trigger the host's immune response, which was speculated to require a "critical antigenic mass".

Lack of surface antigens
Outer surfaces of bacterial pathogens are the first bacterial component to encounter the host and are often the targets of host adaptive immunity. One of most prominent features of T. pallidum is that its cell has only rare integral proteins in its outer membrane, approximately 1% of the number found in the outer membrane of E. coli. The rare T. pallidum outer membrane proteins are likely to be very important in interactions with the host; for this reason, their identity has been the subject of intense research.


Low iron requirements, ability to obtain sequestered iron
Iron sequestration is one of the important defense mechanisms used by the infected host. The host's transferrin and lactoferrin proteins bind free iron making it unavailable to bacteria and impairing their growth. T. pallidum may be able to acquire iron from these host proteins. It may also overcome the iron sequestration by using enzymes that need metals other than iron as their cofactors. In addition it lacks an electron transport chain, which is made up of enzymes that use iron as a cofactor, which decreases its overall demand for iron.

Resistance to macrophages in subpopulation of the pathogen
Opsonizing agents are serum components, antibodies, or the complement protein C3b, which make the pathogen recognizable to macrophages via specific cell surface receptors. T. pallidum antigens, including Tp92 andTprK, have been shown to induce production of opsonic antibodies. Antibodies against the VDRL (Venereal Disease Research Laboratory) antigen, a complex of cardiolipin, cholesterol, and lecithin, also increase the phagocytosis of T. pallidum by macrophages. Majority of treponemes that multiplied in quantities at the site of initial infection usually are cleared by macrophages. However, a small subpopulation of the organisms persists and appears to resist ingestion by macrophages. This phenomenon suggests that opsonic antibodies do not bind these organisms, thus allowing them to survive in the face of active immune clearance.

[To translate: Antibody opsonization is the process by which a pathogen is marked for ingestion and destruction by a phagocyte. Opsonization involves the binding of an opsonin antibody to a receptor on the pathogen's cell membrane. The immune system cannot always eliminate T. pallidum even though it has "recognized" the existence of the disease.]

Resistance to neutralization by antibodies
Besides opsonization, there are other functions of antibodies produced during T. pallidum infection. Antibodies developed against T. pallidum immobilize organisms and block them from binding the host's cells. Administration of whole serum and fractionated IgG from long-term-infected rabbits delays lesion formation in challenged rabbits, but lesions develop at the inoculation site within days of discontinuing the treatment. This demonstrates that specific antibody alone, while inhibitory to the establishment of lesions, is not sufficient to kill T. pallidum and prevent infection.

Orchestrated regulation of expression of antigens
Several genes that encode candidate outer membrane proteins belong to the tpr gene family which contains twelve genes that are divided into three subfamilies I, II, and III). The proteins encoded by tprF, tprI, and tprK are predicted to be located in the outer membrane.

Most of the proteins encoded by the tpr genes (the Tprs) elicit an immune response in experimental syphilis. Antibody responses arise at different times after infection: anti-TprK antibodies are seen as soon as 17 days postinfection and are robustly reactive at day 30, while antibodies against the members of subfamilies I and II often are not detectable until 45 days after infection and reach peak titers at day 60.

The time of development of antibodies to specific Tprs may reveal the timing of expression of the proteins that induced those antibodies. Regulation of expression of related proteins is referred to as phase variation and may be used by T. pallidum to down-regulate the expression of those Tprs against which an immune response has been mounted, while simultaneously up-regulating the expression of new Tprs, which are not recognized by the existing immune response. This strategy may help T. pallidum maintain chronic infection.

Antigenic variation of TprK protein
Recent studies identified TprK as a membrane-localized protein. The tprK gene and predicted protein amino acid sequences are characterized by seven discrete variable (V) regions that are separated by stretches of conserved sequences.

Diverse tprK sequences have been demonstrated between subpopulations of every T. pallidum strain within single host. DNA sequence cassettes that correspond to V-region sequences were discovered in an area of the T. pallidum chromosome separate from the tprK gene. These cassettes are potential sequence donors and are presumed to replace portions of V-region sequences in the tprK gene.

The TprK protein elicits both cellular and humoral immunity in infected animals. Antibodies to TprK that arise in response to T. pallidum infection are specifically targeted to the V regions. Very slight changes of the amino acid sequence in a V region can abrogate the ability of antibodies to bind the V region.

Thus, the host immunity may eliminate organisms that express TprK sequences against which specific antibodies have been developed. Generating new variation in TprK may help pathogens to escape immune recognition and sustain the chronic infection.

Vaccine Development
There is no vaccine for Syphilis. The outer membrane of T. pallidum has too few surface proteins for an antibody to be effective. Efforts to develop a safe and effective syphilis vaccine have been hindered by uncertainty about the relative importance of humoral and cellular mechanisms to protective immunity  and the fact that T. pallidum outer membrane proteins have not been unambiguously identified.

Some Abstracts On Vaccine Efforts

Assessment of cell-surface exposure and vaccinogenic potentials of Treponema pallidum candidate outer membrane proteins
Microbes and Infection
Volume 9, Issue 11, September 2007, Pages 1267-1275
T. pallidum is believed to be an extracellular pathogen and, as such, the identification of T. pallidum outer membrane proteins that could serve as targets for opsonic or bactericidal antibodies has remained a high research priority for vaccine development. However, the identification of T. pallidum outer membrane proteins has remained highly elusive. Recent studies and bioinformatics have implicated four treponemal proteins as potential outer membrane proteins (TP0155, TP0326, TP0483 and TP0956). Indirect immunofluorescence assays performed on treponemes encapsulated within agarose gel microdroplets failed to provide evidence that any of these four molecules were surface-exposed in T. pallidum. Second, recombinant fusion proteins corresponding to all four candidate outer membrane proteins were used separately, or in combination, to vaccinate New Zealand White rabbits. Despite achieving high titers (>1:50,000) of serum antibodies, none of the rabbits displayed chancre immunity after intradermal challenge with viable T. pallidum.

Progress towards an effective syphilis vaccine: the past, present and future
Authors: Cullen, Paul A; Cameron, Caroline E
Source: Expert Review of Vaccines, Volume 5, Number 1, February 2006 , pp. 67-80(14)
Syphilis is a disease caused by infection with the spirochetal pathogen Treponema pallidum subspp. pallidum. Despite intensive efforts, the unusual biology of T. pallidum has hindered progress towards the development of a vaccine to prevent infection. This review describes previous endeavors to develop a syphilis vaccine, outlines the key issues in the field and proposes new directions in the design of a T. pallidum vaccine. Following a brief overview of the disease symptoms, epidemiology, diagnosis and treatment, a case is put forward for the benefit of pursuing a syphilis vaccine. Relevant material concerning immunity to T. pallidum infection is summarized and evaluated, and pilot experiments describing the use of whole-cell bacterin vaccines and similar preparations are included. A detailed section concerning subunit vaccines is provided, incorporating discussions pertaining to relevant antigen selection, the identification of putative T. pallidum surface-exposed outer membrane proteins, factors hindering previous attempts to vaccinate with recombinant outer membrane proteins, problems and pitfalls of syphilis outer membrane protein-based vaccines, anti-attachment vaccines and the potential use of nonprotein subunit preparations as vaccinogens. Subsequently, critical aspects concerning vaccine antigen preparation and delivery are noted, including protein conformation, synergy, post-translational modifications, live attenuated organisms as vaccine vectors, prime–boost methodologies, adjuvant selection and immunization routes. Finally, animal models are discussed with particular reference to immunoprotection studies. A more thorough understanding of immunity to syphilis, a comprehensive assessment of the immunoprotective capacity of the putative surface-accessible antigens of T. pallidum and utilization of the latest advances in vaccine science should set the scene for future development of a syphilis vaccine.

LUKEHART SA; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chem other Intersci Conf Antimicrob Agents Chem other. 2000 Sep 17-20; 40: 540.
Univ. of Washington, Seattle, WA
Syphilis is a major public health problem in developing countries and in certain regions of the United States. It is estimated that there are twelve million new cases of syphilis per year, and at least 25 million infected persons worldwide. Syphilis is a recognized cause of perinatal morbidity and mortality and is a cofactor in acquisition and transmission of HIV infection. Despite the existence of safe and effective penicillin therapy, syphilis is unlikely to be controlled globally without an effective vaccine. Proof of concept for a syphilis vaccine was obtained in 1973, when Dr. James N. Miller demonstrated complete protection against infectious challenge in the rabbit model of experimental syphilis following immunization with gamma-irradiated Treponema pallidum. Since that time, numerous attempts to achieve protection using killed T. pallidum or isolated treponemal antigens have failed to yield satisfying results. Recent efforts have focussed on the identification of antigens that may be exposed on the surface of the intact treponeme, although definitive identification of such molecules has been difficult. This presentation will describe a number of candidate vaccine antigens that are currently under active investigation. Concerns relating to possible lack of heterologous cross-protection will be discussed in light of recent data regarding molecular heterogeneity of strains of T. pallidum

Biological Basis for Syphilis
Rebecca E. LaFond and Sheila A. Lukehart
Clinical Microbiology Reviews, January 2006, p. 29-49, Vol. 19, No. 1
Departments of Pathobiology, University of Washington, Seattle, Washington
Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

Ongoing Research of Dr. Caroline E. Cameron
2006-present University of Victoria, Victoria, BC

The laboratory of Dr. Caroline Cameron focuses upon spirochetal bacteria, with a specific focus on Treponema pallidum and Leptospira. The overall objective of the research is to identify and characterize molecules that are central to the pathogenesis of these important human pathogens.

The first main project investigates the extremely invasive nature of T. pallidum. Within our laboratory we have discovered several adhesins that contribute to T. pallidum attachment and a protease that is central to dissemination within the host. We are currently developing methods to target these proteins, with the ultimate goal of developing a prophylactic intervention to prevent the establishment of chronic infection.

The second major project within the laboratory involves the identification of novel diagnostic antigens, and the translation of this research into an improved syphilis diagnostic test.

We also perform proteomic analyses of Treponema pallidum to identify potential surface-exposed proteins within this unculturable pathogen.

The long-term objective of the research performed within the laboratory is to expand our knowledge of spirochete pathogenesis, which will in turn allow for the development of novel therapeutic reagents and/or preventative measures to combat infection. Future research will investigate the role of identified virulence factors in the pathogenesis of T. pallidum and Leptospira.

Citations
[1] Infectious Diseases Society of America (2009, October 23). Syphilis Survey Reveals Need For Accurate Testing For Early Infection. ScienceDaily. Retrieved January 13, 2011, from http://www.sciencedaily.com­ /releases/2009/10/091022122334.htm
[2] Stevenson, J., & Heath, M. (2006). Syphilis and HIV infections: An update. Dermatol Clin, 24(4), 497.
[3] Peterman, T., Heffelfinger, J., et al. (2005). The changing epidemiology of syphilis. Sex Transm Dis, 32(1), S4.

Other citations also expanded upon from: Metapathogen and http://en.wikipedia.org/wiki/Syphilis



I'm guessing that for most of you, this is more than you ever knew about Syphilis or cared to know about it.

It's a start, really. There's more.

Think about everything you've read here, and anything you've read about Borrelia burgdorferi. There are differences and then there are similarities. They can't be treated interchangeably, but it is useful to look at the issues involved with both, where they do overlap, and how they've been approached in research. And also why each has been approached in research the way it has.
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Tuesday, January 11, 2011

2 Brief remarks on an older post about forum rules

I am somewhat puzzled that of all that I have posted here thus far, a post on forum posting rules I do not understand is one that continues to get a fair number of hits.

Why do people think this post is so interesting? I think Kary Mullis' Altermune research is way more interesting than that. To each his own, I guess.

Anyway... I've revisited this issue on a forum thread recently, and those who responded seemed to have not read what I wrote in the first place, and responded that I should know why LLMDs need to have their identities protected and know about the film, Under Our Skin.

I do know about why, and I have seen the film. Twice. I had a copy of the disk, which is now in the hands of a therapist who counsels people with disabilities and chronic illness.

Since my point seems to have gotten lost somehow, I will explain what I think about forum posting rules about LLMDs here once more in more abbreviated terms:
It seems to me that it makes more sense to use the term "My LLMD" or "My MD" when posting to a forum about someone giving me medical treatment, and more sense to use the term "An LLMD" or "An MD" when posting about a medical doctor who is not mine. 
Given that there is a small number of doctors who are LLMDs, I do not think that using an initial alone or an initial and a state is adequate privacy - if your goal is privacy. Those who are familiar with doctors who have already been in the spotlight may figure it out, and those who are patients may try to figure out which doctor is being discussed. 
Other mailing lists have used the above approach with great success and it removes confusion over what posters should do.

My rules for my own blog are somewhat modified to allow for mentions in the media and publications.

Alrighty then.


Next post coming up: An overview of Syphilis and vaccines

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Sunday, January 9, 2011

1 When will the media ask more of the right questions about antibiotics and vaccines?

I was originally going to title this post, "Why is the media drinking the Kool-Aid?", but then I thought better of it, and changed the title after recalling a well-written post on that phrase.

So, my original question stands: When will the media ask more of the right questions?

When I reflect on the media's approach to the issue of Chronic Lyme disease, it seems they almost completely side-step the issue of Lyme Disease and infectious diseases and their treatment in general.

Dear media, where is your sense of curiosity? Your ability to dig deeper into the issues? Your investigative reporting chops?

We begin with the old question by many Lyme patients of course, which is this:

"If Lyme Disease can be cured with 21-28 days of antibiotics, why are researchers working on a vaccine?"

A simple question. That would be a good start.

"If - as the official story claims - the Lymerix vaccine was pulled from the market because of low sales, why develop another vaccine?"

Okay. Not bad. Also a good question. Most readers will wonder this, too, once they realize Lyme Disease actually had a vaccine on the market around 1999, but it was pulled off the shelves.

But let's keep going, shall we? Indeed...

"If another spirochetal infection, Syphilis, is spread by sexual contact and is on the increase - why isn't more research going into developing a vaccine for Syphilis instead?"

If Lyme Disease is - as claimed by the IDSA and some medical professionals - so rare and hard to catch (even though, uh, the CDC says it is the fastest-growing vector-based disease) - then why isn't more money and research going into vaccines for common sexually-transmitted infections such as Syphilis?

Syphilis is seriously on the rise in the past several years, and it suffers from some similar treatment and diagnostic issues Lyme does - such as some people who are acutely infected do not get a visible chancre or sore signaling its presence (some people with acute Lyme never get a rash).

It's proven Syphilis is sexually-transmitted and congenitally-transmitted. With that in hand and no controversy over it, shouldn't there be a vaccine for it?

That's a better question, isn't it?

The short answer to why there is no Syphilis vaccine yet is that people are working on this problem, but they haven't come up with a solution. Why this is the case is a bit complicated (I will attempt to lay it out here some time in another post), but I am surprised the media hasn't jumped on this more.

Okay, let's try this one:

"If the IDSA is concerned about antibiotic resistance and not enough funding for R & D of new antibiotics, could this be pushing them down the route of more vaccine development in general and not just for Lyme Disease?"

Ah.

Now we're talking. Very good question.

Now this starts sucking in the broader issues of politics and epidemiology and the soaring costs of healthcare.

According to the IDSA's 2010 testimony to the House Committee on Energy and Commerce Subcommittee on Health, more funding is needed for new antibiotics or everyone is in deep, deep trouble due to growing antibiotic resistance and lack of development of new antibiotics.

Entire fields of application of antibiotics will have to be more carefully scrutinized and medicine stringently doled out until new antibiotics are developed that evade resistance.

The use of antibiotics for acne treatment and indiscriminately for ear and sinus infections may be put to a standstill.  And yes, using antibiotics in factory farms has also been mentioned by the IDSA as something that needs reducing, too.

Tuberculosis? I think they'll draw the line there, but continue to also work on a Tuberculosis vaccine.

In their testimony, the IDSA states:
"The ESKAPE Pathogens: The so-called ESKAPE Pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and ESBL positive bacteria, such as E. coli and Enterobacter species) represent a grouping of antibiotic-resistant gram-positive and gram-negative bacteria  that cause the majority of U.S. HAIs (Health-care Associated Infections). The group is so-named because these bacteria effectively “escape” the effects of most approved antibacterial drugs."

Right now, MRSA and its even more evil sister, VRSA (so far, extremely rare with only 11 documented cases in the US, VRSA is the worst staph infection possible - because even vancomycin won't beat it), are the IDSA's top targets. Followed by that long list above - many hospital-acquired infections, but some community-acquired.

There's more:

"Clostridium difficile: Another resistant infection receiving increased scrutiny is Clostridium difficile (C. diff). C. diff. is an HAI that can lead to severe diarrhea, rupture of the colon, kidney failure, blood poisoning, and death. CDC estimates there are 500,000 cases of C. diff. infection annually in the U.S., contributing to between 15,000 and 30,000 deaths. States have reported increased rates of C. diff. nationwide over the past several years noting more severe disease and an associated increase in mortality. Elderly hospitalized patients are at especially high risk."

Well, none of us want that, either. Either as a public health crisis or as a personal one after I've taken months of antibiotics.

But it's useful to know that this is being mentioned before Congress and this is part of a bigger picture.

Does anyone here know about The STAAR Act, H.R. 2400? No? Doesn't sound familiar?

I did a quick search of Lymenet, Lymenet Europe (although it's not pertinent to them, they may want to watch what happens in the US), and googled it using the keywords, "STAAR Act H.R. 2400 Lyme Disease" in varying combinations. Neither of those two forums turned up a hit, and my last search on Google netted one result within seven pages of results for the blog of a Lyme patient from Utah.

This act should be more familiar to you all, because the STAAR Act stands for "Strategies to Reduce Antimicrobial Resistance".

Taken from the final 2010 report from the IDSA to the House Committee on Energy and Commerce Subcommittee on Health:

"The STAAR Act strengthens existing efforts by establishing an Antimicrobial Resistance Office (ARO) within the HHS Office of the Assistant Secretary of Health. The Director of ARO will serve as the director of the existing interagency task force. The Act also establishes a Public Health Antimicrobial Advisory Board (PHAAB) comprised of infectious diseases and public health experts who will provide much-needed advice to the ARO Director and task force about antimicrobial resistance and strategies to address it. The STAAR Act will strengthen existing surveillance, data collection, and research activities as a means to reduce the inappropriate use of antimicrobials, develop and test new interventions to limit the spread of resistant organisms, and create new tools to detect, prevent and treat drug-resistant “bad bugs.”"
And that's just part of it, really - you ought to read the entire report.

One of the IDSA's broader goals beyond this act is to institute a special fee called "the Antibiotic Innovation and Conservation Fee" on every course of antibiotics used by doctors and veterinarians in the future - both to acquire money for funding new antibiotic development - and to encourage restricted and judicial use of the antibiotics remaining in use. And then there is also the proposal for an "antibiotic stewardship program" which will be intended to track and reduce usage of antibiotics as well as lower medical cost.

Now, before you get all psyched out about all this, keep this bit in mind which is a double-edged sword:

The CDC and the IDSA have a major fiscal shortfall for Fiscal Year 2011. Cited from the IDSA's own website...
"Especially hard-hit in this year’s budget is CDC, which would have its budget cut by $135 million. Of particular concern to IDSA are:
  • the slashing of CDC’s Infectious Diseases program budget, which would be cut by almost $100 million, a 5 percent decline
  • a cut of more than 50 percent to the already strapped budget for the vital Antimicrobial Resistance program, which would force CDC to cut in half its support for state and local surveillance, prevention, and control efforts, and end all grants to states for the successful Get Smart in the Community program to combat improper antibiotic use
  • a 21 percent reduction in grants for the Section 317 immunization program compared to the current fiscal year, in light of the end of additional funding provided though the stimulus bill; these cuts will reduce access to immunizations, which save lives and millions of dollars in preventable medical spending
While infectious diseases research at the National Institutes of Health (NIH) would grow by $150 million in FY2011 under the proposed budget, this represents just over 3 percent above current funding levels. With biomedical research inflation increasing about 3.6 percent per year, this budget will actually result in fewer grants awarded and fewer new research projects, at a time when the need for this research is so critical."
As soon as there is any money, you can imagine where the IDSA wants at least some of it to go.

The double-edged sword is that even as antibiotic treatment may continue to be under less scrutiny, there isn't funding for new antibiotics to be developed.  This happens while the IDSA has proposed that 10 new antibiotics be developed by 2020.

This all brings up a few questions for me right now, having read all this:

Why is the NIH getting more money in 2011 and why is the CDC's budget getting cut?

When the IDSA's budget has been cut and it's facing increasing antibiotic resistance in society as a problem - are they going to advocate that those with acutely deadly infections get antibiotics first - while those with chronic infections that take longer to kill get antibiotics last?

When the IDSA's budget has been cut and more people are dying from MRSA and there's been few new antibiotics for years, when push comes to shove, does the IDSA start focusing more on vaccines alongside pushing for funding for new antibiotic research?

I have a feeling the reason the media doesn't ask more of the right questions is that they lead to even more questions - and answers that do not fit into a sound bite.

What's happening here? Anyone reading this know more about this stuff? 


Anybody have more recent information on this than me and google in a few minutes?
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Saturday, January 8, 2011

0 Pain & Suffering

I'm in more pain lately. Suffering. Not drinking the scotch. Yet.

This brings something to mind that I saw last year, and if you've suffered a lot of pain, perhaps you can relate to it...

There is this hilarious writer, Allie Brosh, who draws manic childish drawings to illustrate her stories for her site, "Hyperbole and a half".

In this story about her boyfriend, she talks about how the original "faces of pain" scale in the doctor's office and ER is inadequate to describe pain, and creates her own.

I'm posting an image of part of her version of the "faces of pain" scale here, and I recommend reading her entire post on the scale - believe me, just seeing the image alone does not give you a sense of her post. You also might want to check out other posts Allie Brosh has made...



PS: My pain is between a 6 and a 7 as of this writing, but you'd have to go to her pain scale post to see exactly what that means...
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Friday, January 7, 2011

Thursday, January 6, 2011

0 TED Talk: Aiding the immune system to fight infection

I caught this talk recently on TED that was more of a teaser for me. I found it interesting and wanted to share here.

About this TED Talk

Drug-resistant bacteria kills, even in top hospitals. But now tough infections like staph and anthrax may be in for a surprise. Nobel-winning chemist Kary Mullis, who watched a friend die when powerful antibiotics failed, unveils a radical new cure that shows extraordinary promise.(Recorded at TED 2009, February 2009 in Long Beach, California. Duration: 4:35)



[ More here, in an interview with Kary Mullis. ]

So, in case you didn't know, in the early 1980s, Kary Mullis developed the polymerase chain reaction (PCR), which is a way of making copies of a DNA strand using the enzyme polymerase and some basic DNA "building blocks." Mullis shared the 1993 Nobel Prize in Chemistry for developing this technique.

But Mullis has moved on to doing research on chemically programmable immunity using Altermune technology.

Altermune, LLC, in collaboration with Ron Cook of Biosearch in Novato, CA, re-directed antibodies whose job used to be binding to something called the alpha-Gal epitope or galactose-alpha-1,3-galactosyl-beta-1,4-N0-acetyl glucosamine (now say that three times fast, I dare you) to influenza using DNA aptamers attached to the alpha-Gal epitope.

These linkers can grab influenza virion and turn it over to a human macrophage, which gobbles it up. Testing was done using a drug that can be inhaled.

Altermune is currently focusing on Influenza A and drug resistant Staphylococcus aureus.

This is fascinating.

Programming your own immune system to more effectively fight infections.

I've been wondering what other technologies we could use to combat infection and avoid the issue of antibiotic resistance, which is becoming more crucial as there has been little in the way of new antibiotic research and development during the past decade.

If Kary Mullis can help us use our own immune systems to effectively fight infection, maybe we can not only avoid resistance - but the side effects of many antibiotics and antiviral medications as well.

I'm sure there are some drawbacks and kinks to work out. I'm wondering, for example, how this technology handles transfections. I need to replay the entire TED talk and watch it again, and read the research.

In the meantime, if you are up to the task, here is a more technical Powerpoint presentation on Altermune I have found online:

www.bibalex.org/supercourse/supercoursePPT/37011-38001/38071.ppt

Note of bizarreness: Read the comments on the original TED post. Apparently Mullis is an AIDS denialist? Does anyone know about that?

Dig out your googling chops... the more you learn about Mullis, the more bizarre his story becomes.
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