1 Three Notable NIAID 2012 Research Projects On Lyme Disease

The National Institute of Allergy and Infectious Disease (NIAID) is conducting some Lyme disease related research which I think readers should know about. There are a number of projects to be found on the Project Reporter web site which may be fascinating, but I took the time to select and highlight a few projects which would be of greater interest to patients suffering with Lyme disease and/or its coinfections.

Project: AN INTRACELLULAR NICHE FOR BORRELIA BURGDORFERI
Institution: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
PI: Skare, Jonathan

Description (by applicant):

Lyme disease, caused by the spirochetal bacterium Borrelia burgdorferi, is the leading arthropodborne infection in the United States and causes significant morbidity in endemic areas. If untreated B. burgdorferi can persistently infect individuals even though the host mounts a potent adaptive immune response such that antibodies obtained from infected patients or experimentally infected animals effectively kills in vitro cultivated B. burgdorferi. In addition, a robust cell-mediated proinflammatory response is observed that induces IL-6, IL-12 and IFN- and inhibits IL-10. Furthermore, the spirochete can resist complement killing demonstrating that this important component of the innate immune response is not sufficient to eliminate B. burgdorferi infection.

The observation that B. burgdorferi persists in such a hostile environment indicates that the spirochete is adept at evading the host immune response via mechanisms that have not been completely elucidated. One possibility is that B. burgdorferi invades host cells and survives at low levels. Recently we have determined that B. burgdorferi invade both immortalized and, more importantly, primary cells (both fibroblasts and endothelial cells) and persist as viable cells in o-culture. In addition we have preliminary data suggesting that the ability to invade host cells involves both integrin binding and Src kinase activity.

In this application we propose to further characterize the internalization of B. burgdorferi and track the fate of B. burgdorferi within thes infected cells to determine how they affect the localized host response following infection. To accomplish this we will use both in vitro correlates of invasion and intracellular survival as well as in vivo imaging of experimentally infected mice as readouts for our studies.

Specifically, we propose to:

(1) Characterize the invasion of Borrelia burgdorferi into primary fibroblasts. The working hypothesis here is that B. burgdorferi exploits invasion as an additional mechanism to avoid host clearance. Our preliminary studies demonstrate that B. burgdorferi invasion is not dependent on host fibronectin, but does involve B1 integrins other than a5B1. In this Aim we will identify the subunit that pairs with B1 to promote invasion and will also evaluate how B. burgdorferi traffics within these cells; and

(2) Determine if invasion is required for B. burgdorferi persistence in vivo. Our working hypothesis is that invasion contributes to persistence by providing an immunoprotected niche for B. burgdorferi. Since Src kinases are required for borrelial internalization in vitro, we will determine whether Src kinase inhibitors alter the infectivity potential of B. burgdorferi in vivo. In addition to standard cultivation and molecuar approaches, novel in vivo imaging will be employed to assess how the inhibitor affects colonization.

The overall goal of these studies is to determine the extent in which an intracellular locale contributes to borrelial persistence.

PUBLIC HEALTH RELEVANCE: Borrelia burgdorferi, the etiologic agent of Lyme disease, is the most common arthropod-borne infectious agent in the United States, and, as such, represents an important Public Health issue. The studies described in this application are designed to address how B. burgdorferi is able to persist effectively in infected mammals despite effective innate immune killing mechanisms and a potent adaptive immune response directed against this pathogen. The hypothesis being tested herein is that B. burgdorferi is capable of low-level intracellular survival in non-immune cells as an additional strategy to prevent borrelial host clearance.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8300386&icde=12284856

Comment: This really begins fulfilling my wishlist, and I look forward to the imaging study videos that I hope will be made and posted online. If there is some sort of confirmation of intracellular Bb in vivo this may explain why some patients need additional antibiotics and why existing treatments may be inadequate as a matter of timing.

This next project is bound to generate discussion, as it involves the potential role of toxins in Borrelia burgdorferi. In this case, the researcher is looking for gene clusters in Borrelia burgdorferi which may create cytolysins similar to the toxins which are found in Staphylococcus aureus, Listeria monocytogenes, and Clostridium botulinum.

Project: A COMMON DENOMINATOR OF PATHOGENESIS; A RARE OPPORTUNITY FOR NOVEL THERAPEUTIC DE(VELOPMENT)
Institution: UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN
PI: Mitchell, Douglas

Description (by applicant):

Abstract: The 20th century witnessed several major advances in medicine. Perhaps most important were the discovery of antibiotics for bacterial infections and effective vaccines for several major viruses. Unfortunately, the creation of effective vaccines for bacteria has lagged behind analogous anti-viral strategies. Compounded with the rise in antibiotic resistance and a lack of interest from the pharmaceutical industry in pursuing novel antibiotics, we risk losing the fight against bacterial pathogens.

Described herein is an unconventional strategy to exploit bacterial toxins as both novel targets for antibacterial agents and antigens for vaccine development. To intelligently address the increasing threat posed by bacterial pathogens, more effort is needed to uncover the molecular underpinnings of virulence. Our group specializes in the use of bioinformatics, in vitro reconstitution, and genetic manipulation to identify and characterize gene clusters that are responsible for the biosynthesis of virulence-promoting cytolysins. The best-known toxin in this family is the highly modified peptide, streptolysin S (SLS, produced by Streptococcus pyogenes).

SLS production is required for the infective process, but not essential life processes. Our work has uncovered SLS-like toxins are synthesized by at least three other notorious human pathogens, including Staphylococcus aureus, Listeria monocytogenes, and Clostridium botulinum. We aim to study the potential role of the SLS-like toxin in an additional organism, Borrelia burgdorferi (Bb), which causes Lyme disease.

Although widely known, the Bb molecular mechanism of pathogenesis is inadequately defined. If the SLS-like toxin was indeed employed during Bb infections, this would represent the first demonstration of toxin utilization in this family of organisms and would prompt a major revision of borrelioses.

Because bacteria typically employ disparate pathogenic mechanisms, the conserved, SLS-like pathway provides a rare opportunity to develop more broadly applicable, yet targeted countermeasures. From our perspective, new antimicrobial strategies should directly target the pathogenic mechanism, rather than DNA replication, protein synthesis, or the cell wall. This approach holds enormous potential, as these drugs will theoretically be resistant to resistance.

This project will identify inhibitors of SLS toxin biosynthesis for the specific purpose of developing novel antibacterials. Moreover, SLS is non-immunogenic, rendering it an unfeasible candidate for vaccine development.

We have succeeded in generating attenuated variants with the anticipation that these can be used for raising toxin-neutralizing antibodies. The notion of immunizing against a bacterial toxin represents a potentially general strategy for future vaccine development.

With this proposal, we aim to not only fundamentally shift the accepted view of Bb pathogenesis, but also to challenge the paradigm that antibiotics must kill bacteria and non-immunogenic toxins are intractable vaccine candidates. These seemingly unrelated goals are actually quite intertwined. Our approach rests on the philosophy that a more complete understanding of toxin biosynthetic pathways and chemical structure can be rationally exploited to design novel therapeutics.

Public Health Relevance: Bacterial pathogens employ numerous mechanisms to evade the human immune system. We have discovered a novel strategy within the organism that causes Lyme Disease, who's pathogenesis remains largely enigmatic. A greater understanding of these processes will lay the foundation for developing the next generation of antimicrobial drugs.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8145943&icde=12284856

Comment:

Wait... I thought Radolf & co. said Borrelia burgdorferi does not produce a toxin? I know Donta patented some genes in Bb he saw as being analogous to a toxin.

Is there now evidence of newly researched genes which create a toxin in Bb? Or is this an old hypothesis which is being revisited?

Project: ASSESSMENT OF PATIENTS WITH BORRELIA INFECTION
Institution: NIAID
PI: Marques, Adriana

Description (by applicant):

Lyme disease is a multisystem illness caused by infection with the spirochete Borrelia burgdorferi and it is the leading vector-borne disease in the United States. Our current work addresses the following areas in Lyme disease: development of new tests and biomarkers for infection, investigation of persistence of infection with B. burgdorferi in humans, search for the cause of Southern Tick-associated Rash Illness (STARI), and investigation of the role of immune response in Lyme disease and PLDS.

One of the main problems in Lyme diagnosis has been the lack of highly specific and sensitive assays for B. burgdorferi and the lack of a test that could be used to assess response to therapy. Such assays should greatly facilitate the accurate diagnosis of Lyme disease and assessment of response to therapy in individual patients. Currently, no such test is available.

We have developed a new test using the luciferase immunoprecipitation systems (LIPSs) for profiling of the antibody responses to a panel of B. burgdorferi proteins for the diagnosis of Lyme disease. A synthetic protein consisting of a repeated antigenic peptide sequence, named VOVO, had the best diagnostic performance, similar to the C6 test (a diagnostic test using a peptide ELISA that we have helped develop and is highly sensitive and specific). The VOVO LIPS test displays a wide dynamic range of antibody detection spanning over 10,000-fold without the need for serum dilution; and offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease.

Recent studies have shown that B. burgdorferi may persist in animals after antibiotic therapy and can be detected by using the natural tick vector (Ixodes scapularis) to acquire the organism through feeding. Whether this occurs in humans is unknown.

We have implemented a new clinical protocol to investigate the utility of this approach for identifying persistence of B. burgdorferi in treated human Lyme disease.

STARI is a rash similar to the rash of Lyme disease that occurs in persons residing in southeastern and south-central states and is associated with the bite of the lone star tick, Amblyomma americanum. The cause of the rash is unknown, as it is the natural course of the disease.

We have a clinical protocol to investigate the cause of STARI, and we are applying new genomic tools that identify bacteria based on species-specific sequences in the 16S rRNA ribosomal genes to the skin biopsies from patients with STARI.

Inflammatory innate immune responses are critical in the control of early disseminated infection, while adaptive immune responses are vitally important, particularly the humoral immune response, in controlling spirochete levels in tissues and resolution of Lyme arthritis in animal models. We are examining the antibody response to immunogenically dominant antigens of B. burgdorferi in PLDS patients and controls.

Further investigation of the anti-borrelia immune response may help in elucidating the pathogenic mechanism of PLDS and yield important information for future approaches to diagnosis and treatment. We have a clinical protocol in which we use DNA microarrays to characterize gene expression patterns in skin biopsies from individuals with EM, with the aim of capturing the human host response to pathogen exposure.

We are also investigating the differences in immunological response between predominantly lymphocytic meningitis and predominantly neutrophilic meningitis. Results from these studies will serve as a window into the fundamental biology of the infection.

Link: http://projectreporter.nih.gov/project_info_description.cfm?aid=8336099&icde=12284856

Comment:

The existence of the VOVO LIPS test is nothing new - reports on the development of this test have been around since 2010. Also, there is already information about a chronic Lyme disease xenodiagnosis study out there.

It seems like this project has a large scope - or consists of more than one project under the same umbrella. So far, no project end date has been posted for this entry.

What would be of most interest to me would be finding differences in immunological response between patients with acute Lyme disease and those with assumed PLDS - something Alaedini has already been studying.

(Side note: I thought that it was already determined that Borrelia lonestari, a relapsing fever spirochete, was the cause of STARI or Masters disease - did I miss something?)

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2 Looking At Camp Other Blog In A Different Way

I don't know how many of my readers are aware of this feature of  Blogger - not everyone's blog is set up this way, where you can change how you view the content.

Try this link out for fun: http://campother.blogspot.com/view/flipcard
(I don't know if it works on mobile; suspect it's web-only)

Note that you can change the format of the blog entries listed by using the pulldown menu in the upper right corner.

I think "flipcard" and "timeslide" are the two best formats, the other ones are not as interesting or useful.

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5 Google Trends On Lyme Disease

I have been having fun with this specialized search tool on Google called Trends, and also an advanced trend tool, Insights. You might want to give them a try here:

http://www.google.com/trends
http://www.google.com/insights

In particular, I've been looking up "Lyme disease" and "Borrelia burgdorferi" and breaking down the search into different data sets by region.

Check this out...

Between 2005 and 2010,  of all worldwide Google searches related to Lyme disease, these were the top keyword searches made:

Notice that most people worldwide have been interested in knowing about Lyme disease symptoms, ticks, and treatment - with tests weighing in at #9.  Some unfortunate people do not know how to spell  "Lyme disease" properly.

Now, take a look at this... Here is a list of the top ten worldwide keyword searches related to Lyme disease which are on the increase between 2005-2010:

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3 Can a computer more accurately diagnose Lyme disease than a human?

I came across this article earlier today, though so far I haven't seen mention of it in the Lyme disease community. (It was published earlier this month, though, so I might have missed it.)

The article, "Just Months After Jeopardy!, Watson Wows Doctors With Medical Knowledge" is about how a computer can make connections between seemingly unrelated symptoms to determine a patient's diagnosis.

In this case, the following scenario and outcome was presented:

"The trainee was sequentially presented the details of a fictitious patient: there’s an eye problem; vision is blurred; the family, living in Connecticut, has a history of arthritis. The trainee’s initial response was uveitis. More clues and the diagnosis was changed to Behcet’s disease until finally the trainee settled on Lyme disease. How sure was this seemingly hasty student of medicine? Seventy-three percent sure."

One important point to be made about the database-based doctor:

"Following its resounding victory on Jeopardy!, IBM’s Watson has been working hard to learn as much about medicine as it can with a steady diet of medical textbooks and healthcare journals. The mock case described above was part of a recent demonstration to the Associated Press showing just how much Watson has learned. The robot’s diagnosis was correct and it identified a link between symptom and cause that was “not common,” as one participating physician called it. After being told the patient was pregnant and allergic to penicillin, Watson suggested treating her with cefuroxine. Its human colleagues agreed."

A striking statement was made further on about how the amount of medical knowledge available doubles every 5-7 years and doctors struggle to keep up with it. This would definitely make the case for having a medical database at one's disposal to assist with diagnosis, but to me nothing is going to replace observation and good old hands-on examinations for many conditions.

We aren't quite at the level of Star Trek probes, but perhaps we're headed that way in the future.

Read more here, at the following link: http://singularityhub.com/2011/06/06/just-months-after-jeopardy-watson-wows-doctors-with-medical-knowledge/

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2 Wolfram Alpha On Lyme Disease Diagnosis

So, I'm not sure how familiar my readers are with Wolfram Alpha. If you've ever heard of the Mathematica software package, these are the guys that created it.

Wolfram Alpha is an online tool that uses computational algorithms and data modeling to output objective information on a variety of topics.

In other words: It takes statistics and facts from numerous sources and creates a database on given topics on the fly.

(To learn more about what Wolfram Alpha's online tool does, go here: http://www.wolframalpha.com/tour1.html)

You can go to their homepage and type any term into their search engine and it will build a page based on that term and nothing but that term. Instead of a list of different link results like you see on Google, you get one page with many different kinds of information on that term or topic.

So for fun, I typed "Lyme disease" into their homepage.

The link for that query is this: http://www.wolframalpha.com/input/?i=Lyme+disease

Now, as part of the output for that query, I received the following table of data:

This is one of those moments where my head is breaking, and I can see where they are drawing their data from in the notes below the table - so I need to follow up and see if I can look at the original source for this data.

But just based on what I'm looking at right now, the words "Oh my god, where are they getting these numbers?" escaped my lips.  

According to the footnote, the data is not CDC based, but is based on actual patient visits to US healthcare providers between 2006-2007. I have to wonder why Wolfram Alpha is mining data from this source and not more recent NAMCS/NHAMCS statistics or another source, but it is interesting to see something that is not CDC for a change.

The data in this table does and does not reflect what I've observed online in the Lyme disease patient community.

For one thing, the chart states far more men than women contract Lyme disease and are diagnosed for it than women.  Yet the number of women I see online who discuss Lyme disease outweighs the number of men a great deal.

After reading Polly Murray's book, The Widening Circle, why women are more active online participants and more activist in general has been made more clear to me: the children. If you are sick with Lyme disease, that's bad enough - but if your child is sick, that's worse, and mothers seem to be more likely than fathers to reach out for answers and support online to help not only themselves but their children. (Sorry dads, I don't like the dissing either, and I'm sure a lot of you are active in your child's health - but statistically speaking more women do end up dealing with their kids' health issues for whatever reason.)

This reaching out and forming support groups began with women way before the internet - the internet is just an extension of what happens in real life.

(By 1992 there were over 100 patient support groups for Lyme disease - which kinda chips away at this idea that Lyme disease is a disease spread by reading the internet. What was the internet in 1992? Usenet?*)

But in this table, it's saying far more men get Lyme disease, and I see fewer of them online.

Okay, so another thing about this table,  just so the reader is clear on what they're reading, it doesn't take 22 doctors for one woman to achieve a diagnosis for Lyme disease here, even though I've heard so many stories about this phenomenon - no, what the table means is that for every 22 office visits a doctor sees, one of them will be a woman that gets diagnosed with Lyme disease. 

That one in six visits for men seems really high to me - too high, if you ask me - but in reading the fine print these are estimates and estimates which are weighted for US demographics (how? in what manner?).

I think what's striking about this one year of data is the extrapolation of just how many patients were diagnosed with Lyme disease over the course of 131,748 doctor visits. 

86,700 people in one year... is that closer to reality than the CDC reported 40,000 or so?

I really don't know how much stock to put in this data at all. I feel like writing Wolfram and asking them what gives. How was the estimation made and weighed and why are they drawing their data from NAMCS/NHAMCS - and if so, can they get more recent data or is this it? 

I'm thinking it would be more accurate a head count to get diagnosis numbers from doctors rather than the CDC, because not all cases are reported - but I don't know how reliable these numbers are or how the estimation was computed.

Update:

Just to add to this, check out this other table generated from the same data set:

Interesting.

Now look at the ratio for the number of  men who are diagnosed with Lyme disease to the number of women.  And now look at the total number of estimated cases. 

The only factor changed for initial data output was from "primary diagnosis at visit" to "any diagnosis at visit". What exactly does this mean?

Update #2:

Well, isn't this interesting. I googled "NAMCS" and my first result was this:

http://www.cdc.gov/nchs/ahcd.htm

On this page, we learn:

"The National Ambulatory Medical Care Survey (NAMCS) is a national survey designed to meet the need for objective, reliable information about the provision and use of ambulatory medical care services in the United States. Findings are based on a sample of visits to non-federal employed office-based physicians who are primarily engaged in direct patient care. 

The National Hospital Ambulatory Medical Care Survey (NHAMCS) is designed to collect data on the utilization and provision of ambulatory care services in hospital emergency and outpatient departments. Findings are based on a national sample of visits to the emergency departments and outpatient departments of noninstitutional general and short-stay hospitals."

So wait. This IS data from a survey the CDC knows about?

What percentage of these diagnosed cases are included in the CDC Lyme disease reported cases?

Why aren't these diagnosed cases mentioned on the reporting page for Lyme disease as a separate category of cases -  even if doctors did not fill out an official report?

Or are they mentioned somewhere on the CDC Lyme disease pages and I've missed it? Anyone want to confirm this for me?

Update #3:

Pointed out by an anonymous commenter on the blog just now - from the same page above:

Wow,  let's give the women lots of Ativan and give the guys none?

After reading this, we're all going to need Ativan.

Where they hell are these numbers coming from, though? The footnote here is really not useful.

And I'm sorry, if I am feeling sick with Lyme disease, getting it up is the last thing that would be on my mind... that must refer to a preexisting drug regimen. Even then... ouch.

I really have to wonder about these numbers.

Update #4 (hopefully the last?):

Okay, so I think I've answered some of my own questions here:
http://www.cdc.gov/nchs/ahcd/ahcd_faq.htm

Q. How are the data used? 

A. NAMCS and NHAMCS data are used to statistically describe the patients that utilize physician services and hospital outpatient and emergency department services, the conditions most often treated, and the diagnostic and therapeutic services rendered, including medications prescribed. The data are used by public health policy makers, health services researchers, medical schools, physician associations, epidemiologists, and the print and broadcast media to describe and understand the changes that occur in medical care requirements and practices. The data are disseminated in the form of public health reports, journal articles, and microdata files. 

Q: Can the ambulatory medical care surveys be used to find out how many people have a certain diagnosis?

A: No. The ambulatory medical care surveys (NAMCS and NHAMCS) are not based on a sample of the population. They are based on a sample of visits rather than a sample of people. The data can be used to find out how many ambulatory care visits were made involving a certain diagnosis. To get an idea of utilization of ambulatory care in the population, the number of visits can be divided by the population of interest to get a rate of visits for a diagnosis of interest.

Okay, partially answered. I still have to wonder how public health policy makers, epidemiologists, etc. use this data, though... and how closely this sample of visits maps to reality.

I really don't think anyone has a true picture of how extensive Lyme disease is and how many people have persisting symptoms of Lyme disease pre- and post-antibiotic treatment, and it would be useful to know how many cases physicians actually diagnose and treat versus report to the CDC as those are different numbers.

Even then, these surveys are only representational of doctor caseloads over a one week period during a given year - they are not solid figures.

* This is not all there was, but there were only 26 web sites in the world at the end of 1992.

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4 Top 10 Tips For Doing Your Own Lyme Disease Research

Here are my top 10 tips to share for doing your own Lyme disease research. Pretty simple and straightforward - and if you have any to add, please share in comments below.

1) Use the scientific, Latin terms for everything. You can use common terms, too, but Latin will give you more results and more specific results.

Examples:

Instead of "Lyme disease" use "Borreliosis".
Instead of "Neuro Lyme" use "neuroborreliosis".
Instead of "Lyme bacteria" or "infection" use "Borrelia burgdorferi".

2) Find out which terms microbiologists and scientific researchers use in their own papers and classes and then apply them to your search.

Examples:

Instead of "coinfection" use "polymicrobialism" or "polymicrobial".
Instead of "can't think straight" use "cognitive symptoms".
Instead of "spinal tap" use "lumbar puncture".
Instead of "shooting and burning pains" use "paresthesia".
Etc. - you get the idea.

Look at online and offline medical dictionaries for words that describe your symptoms and plug those into a search engine.

3)  Move your search away from general Google search to Google Scholar. You can get specific results for only scientific papers and patents that way.


4) Whenever you don't understand a term, use Wikipedia for an explanation.

I add a note of caution here: Wikipedia is not always right, though it usually is correct on basic science definitions.

If you aren't sure, double-check by doing a more general search and rely on college and university web sites for definitions. You may want to restrict your domain search to .edu web sites.

5)  Read educational institution web sites in general.

You may be surprised to find out what research is being done now on Lyme disease and coinfections which hasn't been published yet. Bookmark these items and check PubMed for the university name and researcher(s) name(s) periodically, as a paper will eventually be published.

6) Passively collect research information on your own web site or inbox by using RSS feeds.

If you look at the right column of this page and scroll down, you will see a number of Lyme disease and other disease-related and alternative medicine articles that are directly getting posted to this site all the time.

You can do the same with your own web site - or if you don't have a web site - by using an RSS reader or by subscribing to an RSS feed that gets sent to your email address.

This way, research comes to you and you don't have to always go do a search for it.

7) Look at major professional organizations' web sites - even if you may not agree with everything said - at least you will know what's going on.

Read the IDSA's web site periodically and be aware of how they view the issues around Lyme disease and infectious diseases in general. See what the NIH, CDC, and organizations have to say, and even more, dig deeper and look at what people from those organizations say in their research on PubMed and other online publication hubs. Some of what you find may surprise you.

8) Look at major online science web sites geared towards  a more general audience  (not specifically written for professionals) periodically.

Science Daily is a good example of this, and if you look at the bottom of each article, you will often see a link to the original paper or source on which they based their article. Check out the original source for more information - often it leads to finding out about other research the same researchers did on Lyme disease and coinfections.

Also, use the search function in Science Daily to look up terms such as "Lyme disease", "Borrelia", "Babesia" and even "Malaria". You may find interesting articles and older research from their archives this way.

9) Buy microbiology, acarology, and entomology text books for cheap and used at college bookstores which are trying to get rid of all old textbooks, "fire sales",  Amazon.com, and independent used bookstores near you.

While these textbooks can be dated, you might find information in them that could be useful and give you ideas of where to search next. Note that a lot of the basic information on Lyme Borrelia hasn't changed - but there has been a more refined and detailed understanding of what Borrelia is about over time, though, and those details need to be picked up by reading more recently published papers and books. (I say this, stating that a lot of Lyme disease research I see being cited online for and by patients is a bit outdated - we need to update these sites to reflect the state of the science.)

(You can also see if any friends or relatives have some lying around they're willing to lend or give to you.)

10) Search various libraries online, and participate in your local interlibrary loan program.

Can't afford that $500. book on microbiology? See if you can borrow it through your library's interlibrary loan program.

You will usually have a shorter time limit on borrowing books that are in high demand - some books have to be returned in a week. So if you need more time to work on it, ask someone to copy select passages for you from it to make notes on them later after you return the book.

Also, in many areas you can sign up for a program that will allow others to pick up books for you at the library on your behalf if you are housebound and too ill to go out - see if your area has one and sign up if you need it. This is good program to use in general for any material you may want to borrow for your own personal use.

And a bonus, Number 11:

Have a family member, friend, or friend of a friend who is already studying clinical microbiology, molecular biology, and/or genetics (immunology is helpful, too) help you decipher what you don't understand - and to tell you whether or not they think the findings are significant and which questions are not answered by a particular study that would be useful to have answered.

This may be a tricker bit, because not everyone is going to either have the time to respond to your request for help on this or hold the belief that your research is not worth the effort because they may believe that Lyme disease cannot persist and you are wasting your time.

Unfortunately, this is the truth of it - but in the true spirit of scientific inquiry and basically being stubborn, some people may be willing to help you at least a little bit.

My advice here is the less well-known the person is to you, the better it is to keep personal details out of the query. Also, keep your email or discussion brief, polite, and to the point while avoiding discussing the controversy. This is not to invalidate or dismiss your experience - but being said out of practicality and diplomacy: Busy people are more likely to respond to something in an unbiased fashion if you keep it simple and short.

Happy researching!

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0 Chart: Effectiveness of different alternative medicine ingredients

I found this link on alternative medicine online that you might find interesting:

LINK: A visualization based on the effectiveness of different alternative medicine supplements, spices, oils, and herbs

Each item represented there is based on PubMed and Cochrane reports on large human blind placebo-controlled studies only.

If you click on the bubbles, you'll be taken to abstracts which support the use of those particular alternative medicines for specific conditions.

Note these directions found at the bottom of the page before you go there:

"The higher a bubble, the greater the evidence for its effectiveness. But the supplements are only effective for the conditions listed inside the bubble. (Mouseover the bubble to see what I mean.) 

You might also see multiple bubbles for certain supplements. These is because some supplements affect a range of conditions, but the evidence quality varies from condition to condition. For example, there’s strong evidence that Green Tea is good for cholesterol levels. But evidence for its anti-cancer effects is conflicting. In these cases, we give a supplement another bubble."

The chart is Flash based, but there is a link to a non-Flash version there if you prefer that (iPhone users take heed.)

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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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