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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0 Exercise: A Better Lyme Disease Case Defintion

CDC painting by numbers: The numbers
need to represent reality - actual cases are much
higher than those reported to the CDC.  

Since many patients do not like the case surveillance definition for Lyme disease, I have an exercise for my readers.

I'm going to provide you with a case definition for Lyme Disease, and see what you have to say about it.

Do you think it is better than the current CDC case definition? Or worse? Why or why not?

What do you think needs to change, and how would you change it?

What do you think is missing? What should be added?



Please share your view in comments - I want to see what people say about this provided definition first and then see if we can collectively rewrite a better one.

Lyme Disease

Clinical description

A systemic, tick-borne disease with protean manifestations, including dermatologic, rheumatologic, neurologic, and cardiac abnormalities. The best clinical marker for the disease is the initial skin lesion, erthyma migrans, that occurs among 60-80% of patients.

Clinical case definition

• Erythema migrans, or
• At least one late manifestation, as defined below, and laboratory confirmation of infection

Laboratory criteria for diagnosis

• Isolation of Borrelia burgdorferi from clinical specimen, or
• Demonstration of diagnostic levels of IgM and IgG antibodies to the spirochete in serum or CSF, or
• Significant change in IgM or IgG antibody response to B. burgdorferi in paired acute and convalescent phase serum samples

Case classification: a case that meets one of the clinical case definitions above

Comment

This surveillance case definition was developed for national reporting of Lyme disease; it is not appropriate for clinical diagnosis.

Definition of terms used in the clinical description and case definition:

A. Erythema migrans (EM)

For purposes of surveillance, EM is defined as a skin lesion that typically begins as a red macule or papule and expands over a period of days to weeks to form a large round lesion, often with partial central clearing. A solitary lesion must reach at least 5 cm in size. Secondary lesions may also occur. Annular erythematous lesions occurring within several hours of a tick bite represent hypersensitivity reactions and do not qualify as EM. For most patients, the expanding EM lesion is accompanied by other acute symptoms, particularly fatigue, fever, headache, mild stiff neck, arthralgia, or myalgia. These symptoms are typically intermittent. The diagnosis of EM must be made by a physician. Laboratory confirmation is recommended for persons with no known exposure.

B. Late manifestations

Late manifestations include any of the following when an alternate explanation is not found:

Musculoskeletal system

Recurrent, brief attacks (weeks or months) of objective joint swelling in one or a few joints, sometimes followed by chronic arthritis in one or a few joints. Manifestations not considered as criteria for diagnosis include chronic progressive arthritis not preceded by brief attacks and chronic symmetrical polyarthritis. Additionally, arthralgia, myalgia, or fibromyalgia syndromes alone are not criteria for musculoskeletal involvement.

Nervous system

Any of the following, alone or in combination:

Lymphocytic meningitis; cranial neuritis, particularly facial palsy (may be bilateral); radiculoneuropathy; or rarely, encephalomyelitis. Encephalomyelitis must be confirmed by showing antibody production against B. burgdorferi in the cerebrospinal fluid (CSF), demonstrated by a higher titer of antibody in CSF than in serum. Headache, fatigue, paresthesia, or mild stiff neck alone are not criteria for neurologic involvement.

Cardiovascular system

Acute onset, high-grade (2nd or 3rd degree) atrioventricular conduction defects that resolve in days to weeks and are sometimes associated with myocarditis. Palpitations, bradycardia, bundle branch block, or myocarditis alone are not criteria for cardiovascular involvement.

C. Exposure

Exposure is defined as having been in wooded, brushy, or grassy areas (potential tick habitats) in a county in which Lyme disease is endemic no more than 30 days before onset of EM. A history of tick bite is NOT required.

D. Disease endemic to county


A county in which Lyme disease is endemic is one in which at least two definite cases have been previously acquired or in which a known tick vector has been shown to be infected with B. burgdorferi

E. Laboratory confirmation

As noted above, laboratory confirmation of infection with B. burgdorferi is established when a laboratory isolates the spirochete from tissue or body fluid, detects diagnostic levels of IgM or IgG antibodies to the spirochete in serum or CSF, or detects a significant change in antibody levels in paired acute and convalescent phase serum samples. States may determine the criteria for laboratory confirmation and diagnostic levels of antibody. Syphilis and other known causes of biologic false-positive serologic test results should be excluded when laboratory confirmation has been based on serologic testing alone.


Well, what do you think? What works? What needs rewriting and why?

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13 Books: Borrelia. Plus a lesson in terminology.

Borrelia: Molecular Biology, Host Interaction and Pathogenesis. If you have GB £159 or US $310 on hand, and you want to know the state of the science on Borrelia including Borrelia burgdorferi, afzelii, garinii, and its relapsing fever relatives - this is a good book to get.

If you would prefer to review the book before purchasing - or don't want to purchase it at all - check out your local library's interlibrary loan program.


See a detailed chapter outline at this link: http://www.horizonpress.com/borrelia

I have yet to do a review on this book as it is information dense and takes some time to read through - but I pulled some highlights from the chapter outlines (it is pretty robust for an outline, I have to admit)  and provided some vocabulary translation in which some readers may take an interest:

"B. burgdorferi strain B31, the B. burgdorferi type strain, has been studied in the most detail and harbors twelve linear and nine circular plasmids that comprise about 612 kbp. The plasmids are unusual, as compared to most bacterial plasmids, in that they contain many paralogous sequences, a large number of pseudogenes and, in some cases, essential genes. In addition, a number of the plasmids have features suggesting that they are prophages. Some correlations between genome content and pathogenicity have been deduced and comparative whole genome analyses promise future progress in this arena. [CO comment: Refer to Ben Luft's and Steven Norris' research on Bb strains and their ability to cause infection in human hosts.]"

In general, the whole plasmid thing is just weird. Having plasmids that take up one third of your genome is interesting.

Circular plasmids? No problem. You find them in bacteria all the time.

Linear plasmids? That is a bit unusual. Linear plasmids used to be thought of as only in eukaryotic organisms - organisms with a cell nucleus - not prokaryotic organisms like bacteria. Linear plasmids are also found in viruses. But they are found in few bacteria - Borrelia burgdorferi being one of them.

But prophages...  These are very interesting, and what makes some Borrelia strains more harmful to their hosts. That viral genes end up in Borrelia plasmids is pretty fascinating to me, even though this sort of thing happens with other bacteria too - it's fascinating and adds to Borrelia's existing complexity.

Translation for biology/genetics beginners:

(You might want to check this out sometime: http://en.wikipedia.org/wiki/Introduction_to_genetics .)

chromosome = A chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences.

plasmid  = Usually described as a double-stranded unit of DNA that replicates within a cell independently of the chromosomal DNA. Three of the plasmids found in all Borrelia burgdorferi isolates have been described as "mini-chromosomes".

Your handy little Bb plasmid cheat sheet:
cp = circular plasmid
lp = linear plasmid
cp26 = needed for viability, encodes OspC.
lp25 and lp28-1 = needed for infectivity in mice; lp28-1 involved in antigenic variation.
cp32 = contains prophage material; encodes a BpaB protein, which appears to play a role in replication and segregation.
lp54 = encodes OspA/B operon and decorin-binding protein operon dpbBA

Other Borrelia plasmids (relapsing fever):
cp32 = described in B. hermsii; does not contain an OspE/F/Elp lipoprotein (unlike Bb)

Plasmids make up about a third of Borrelia burgdorferi's entire genome. (Fraser et al, 1997; Casiens et al, 2000). Linear plasmids are the most genetically diverse part of Bb's genome, and rearrangements and deletions inside them contribute to their uniqueness.

In Bb, there is a division of labor between the chromosome and extrachromosomal elements or “plasmids”. Genes encoded on the chromosome tend to do housekeeping - housekeeping genes are present in single copy - while genes on the plasmids tend to be Borrelia-specific, of unknown function or involved in the infective cycle, and present in multiple, related copies.

Source material:
The Prokaryotes: A Handbook on the Biology of Bacteria (Vol. 7) by Martin Dworkin and Stanley Falkow.
The Linear Hairpin Replicons of Borrelia burgdorferi. Kerri Kobryn. Microbiol Monogr (7) Universite de Sherbooke, Sherbrooke, QC, Canada

genome = the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA.

pseudogene = dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell. Also known as mutationally damaged or "Junk DNA" - it is not always necessarily "junk" - its function is simply unknown at this time.

essential gene = genes that are indispensable to support cellular life. These genes constitute a minimal gene set required for a living cell - if they don't work, the organism dies.

paralogous = This one takes a little more explaining...

Homologous gene sequences = the same, where "homo" means "like, similar" and "hetero" means "different, divergent".

For example, in general, if two or more genes have highly similar DNA sequences, it is likely that they are homologous. "Paralogous" means they are homologous gene sequences which are similar but they occupy different positions or locations in the same genome.

Sequence similarity is often seen in organisms that evolved from the same common ancestor. However, sequence similarity may also arise without common ancestry - short sequences may be similar by chance, and sequences may be similar because both were selected to bind to a particular protein, such as a transcription factor. Such sequences are similar but not homologous.

prophage = Okay... This is where things get weird. A prophage is a phage (viral) genome inserted as part of the linear structure of the DNA chromosome of a bacterium. A temperate phage is integrated into the host chromosome or existing as an extrachromosomal plasmid. This is a latent form of a bacteriophage, in which the viral genes are incorporated into the bacterial chromosomes without causing disruption of the bacterial cell.

In other words, a bacteriophage is a virus that lives inside bacteria, and a prophage is viral genetic material that becomes part of the chromosome in the bacteria (see virus to left, injecting its genetic material inside a non-spirochetal bacteria). So, in this case, at some point in time, a phage known as phiBB-1 (also spelled φBB-1) made its viral genes part of Borrelia burgdorferi's plasmids.

In prophages in general, if the host bacteria is damaged, the prophage is excised from the bacterial chromosome in a process called prophage induction. After induction, viral replication begins via the lytic cycle.

Prophages are important agents of horizontal gene transfer, and are considered part of the mobilome.

In many bacterial species, prophages figure prominently in the biology of these cells, often conferring key phenotypes that can convert a non-pathogenic strain into a pathogen. In other words, while it's residing inside the bacteria, the prophage can turn bacteria that is harmless into harmful bacteria.

Such phenotypic changes can include prophage-encoded toxins, bacterial cell surface alterations, or resistance to the human immune system.

Prophage integration into the host genome can inactivate or alter the expression of host genes. In addition to these direct genetic alterations associated with the addition or inactivation of genes, prophages can also alter the phenotype of bacteria at the population level by facilitating the spread of favorable genes through transduction. (transduction = the process by which DNA is transferred from one bacterium to another by a virus.)

Its significance in Borrelia burgdorferi:

It's not discussed much on Lyme disease patient forums, but some strains of Borrelia burgdorferi have had their plasmids invaded by prophages. The presence of those phages - their viral genetic material - can make Borrelia burgdorferi more pathogenic.

phage particles in Borrelia burgdorferi
from Eggers et al

The phiBB-1 prophage is capable of transducing a cp32 between cells of the same isolate and between different Bb isolates. This means this prophage could play a role in the genetic diversity of different Bb isolates.

The structural proteins for phiBB-1 have not yet been identified, and a number of proteins encoded on cp32 have no homologs in any databases outside of Bb.

cp32 expresses a few outer surface or membrane proteins, of which ospE is the only one of which its function is known. It binds to complement factor H and helps Bb evade the complement system of the host.

A number of different bacteriophages have been observed in association with spirochetes and are being researched now. It may contribute to Lyme disease's ability to persist.

Well-known research on this includes this study:
Eggers et al http://www.ncbi.nlm.nih.gov/pubmed/11466280

Source material:
Wikipedia: http://en.wikipedia.org/wiki/Prophage
Wikipedia: http://en.wikipedia.org/wiki/Introduction_to_genetics
Borrelia: Molecular Biology, Host Interaction and Pathogenesis.
The Prokaryotes: A Handbook on the Biology of Bacteria (Vol. 7) by Martin Dworkin and Stanley Falkow.

pathogenicity = the ability of a pathogen to create infectious disease in an organism.

One of the relevant points to be gleaned from the above is that the genetic makeup of the plasmids are related to the virulence and pathogenicity of Borrelia. (virulence = the degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host.)

"The highly unusual segmented genomes of Borrelia species can contain over 20 autonomously replicating DNA molecules. Many of the molecules, including the chromosome, are linear with covalently closed hairpin ends. Current knowledge of the replication and maintenance of DNA molecules will be reviewed, including the process of telomere resolution, whereby the covalently closed hairpin ends are generated from replicative intermediates. Finally, the proposal that reverse telomere resolution is the driving force shaping the ongoing rearrangements and telomere exchanges in the linear replicons of Borrelia species will be discussed."

Translation for biology/genetics beginners:

chromosome = A chromosome is an organized structure of DNA and protein that is found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences.

nucleotide = molecules that when joined together make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism.

covalently closed hairpin ends = strands of genetic material curve back on itself in a hairpin pattern.

telomere = a region of repetitive DNA at the end of a chromosome, which protects the end of the chromosome from deterioration. The telomere shortening mechanism normally limits cells to a fixed number of divisions, so a shorter telomere means there are fewer divisions left for that cell and it will die sooner. Animal studies suggest that this is responsible for aging on the cellular level and sets a limit on lifespans.

telomere resolution = when the replicated linear DNA ends are processed by DNA breakage followed by joining of DNA free ends to the complementary strand of the same DNA molecule.

reverse telomere resolution = when linear DNA cleaves (splits) and joins hairpin telomeres on unrelated (rather than related) DNA molecules. The new linked plasmid structure could fuse to another linear plasmid in the future, and this explains how Borrelia can engage in telomere exchanges. This process may play a major role in the development of weird linear plasmids in Borrelia and their ability to confuse the immune system.

replicon = a DNA molecule or RNA molecule, or a region of DNA or RNA, that replicates from a single origin of replication. For most prokaryotic chromosomes, the replicon is the entire chromosome.

This part, I think most readers will know about the last sentence - but suspect they will be less familiar with the first half:

Borrelia are not Gram-positive...  But... they are not exactly Gram-negative bacteria, either.

"Although Borrelia spirochetes are often, but mistakenly described as Gram-negative bacteria due to their diderm, i.e. double-membrane envelopes, a closer examination reveals significant differences in composition and architecture. Probably most striking is the lack of LPS, the presence of major surface lipoproteins at the host-pathogen interface during transmission, persistence and ensuing pathogenic processes and the additional function of periplasmic flagella in defining cell shape. While surface lipoproteins such as the Osps interact with a variety of ligands in different organ tissues, they are also targets of the immune response and several have emerged as vaccine candidates."

I found information confirming the fact that Borrelia is not Gram-negative or Gram-positive. It's its own special thing:

Borrelia were thought to be Gram negative because of their double membrane structure, but genetic analysis places them - along with other spirochetes - into a separate eubacterial phylum. Ultrastructural molecular and biochemical studies have emphasized the wide taxonomic gap between spirochetes and Gram-negative bacteria. ( The Genus Borrelia. Melissa Caimano. Prokaryotes (2006) 7:235-293.)

Translation for biology/genetics beginners:

Gram-negative = Gram-Negative Bacteria are simply called this because of their detection by the Gram’s Stain test in which they do not retain the crystal violet color (dye) in their cell wall. The Gram-Negative bacteria cell-wall holds the pink or reddish dye once a counterstain chemical is used. This is characteristic of bacteria that have a cell wall composed of a thin layer of a particular substance (called peptidoglycan).

diderm = double-membrane envelope consisting of an inner cytoplasmic membrane and outer membrane found in Gram-negative bacteria.

double-membrane envelopes = See the picture to the left. Monodermic bacteria (mono = one) have one membrane, and didermic bacteria have two (di = two) membranes - the inner membrance (cm) and outer membrane (om).


LPS = Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals. [CO comment - a question for my readers: If Borrelia burgdorferi do not have LPS, what is producing the endotoxins everyone in the Lyme patient community says are important to detox? Keep reading, the answer is downstream...]

lipid = Lipids are a broad group of naturally occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The main biological functions of lipids include energy storage, as structural components of cell membranes, and as important signaling molecules. In this context, lipids make up the inner membrane of Borrelia burgdorferi.

polysaccharide = Polysaccharides are polymeric carbohydrate structures, formed of repeating units (either mono- or di-saccharides) joined together by glycosidic bonds. Examples include storage polysaccharides such as starch and glycogen, and structural polysaccharides such as cellulose and chitin.

lipoproteins = A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins and toxins are lipoproteins.

(a) external side view of Borrelia burgdorferi spirochete,
(b)  head-on view of cross-section of Bb, and (c)
side view of cross-section of Bb's diderm membranes.  

periplasmic = The periplasmic space or periplasm is a space between the inner cytoplasmic membrane and external outer membrane of Gram-negative bacteria or the equivalent space outside the inner membrane of Gram-positive bacteria. It may constitute up to 40% of the total cell volume in Gram-negative species, and is drastically smaller in Gram-positive species.

flagella = A flagellum is a tail-like projection that protrudes from the cell body of certain prokaryotic and eukaryotic cells, and functions in locomotion. (Flagella is plural of flagellum.)

Osps = Outer surface proteins. The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) that have been characterized (OspA through OspF). The Osp proteins are lipoproteins anchored by N-terminally-attached fatty acid molecules to the membrane. They are presumed to play a role in virulence, transmission, or survival in the tick.

ligand = Any substance (e.g. hormone, drug, functional group, etc.) that binds specifically and reversibly to another chemical entity to form a larger complex.

"Several borrelial proteins have been implicated in adherence to host cell surface proteins and extracellular matrix components and are likely to be involved in the homing of Borrelia to histologic compartments within each tissue, penetration of blood vessels and adherence to and migration through endothelial cells and tissue strata at distant sites. Activation of plasmin on the bacterial surface and induction of host proteases are thought to facilitate dissemination and/or inflammation. Most tissue damage appears to result from host inflammatory reactions. Although the mechanisms are not entirely understood, induction of cytokine/chemokine expression by bacterial lipoproteins and the resulting recruitment and activation of lymphocytes, macrophages and granulocytes play a major role in both local histopathology and constitutional symptoms. Despite their relatively low densities in tissues, Borrelia cause neurologic, cardiovascular, arthritic and dermatologic manifestations during the disseminated and persistent stages of infection by mechanisms that remain largely a mystery. Immune evasion mechanisms, including the vls antigenic variation system, complement-regulator acquiring surface proteins (CRASPs), down-regulation of highly antigenic surface proteins (such as OspC) and invasion of protective niches, permit the survival of the pathogens for months to years following infection despite robust antibody and cellular responses."

Translation for biology/immunology/genetics beginners:

host cell surface proteins = proteins on the surface of the host's cell.

extracellular matrix = Any material produced by cells and secreted into the surrounding medium, but usually applied to the noncellular portion of animal tissues. In other words - the space around the outside of cells, but not within cells.

histologic = related to cells and tissue on the microscopic level.

endothelial cells = cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall.

plasmin = an enzyme present in blood that breaks down many blood plasma proteins, most notably, it breaks down fibrin clots (blood clots).

protease = an enzyme that breaks down proteins.

cytokine = small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication.

The term "cytokine" has been used to refer to the immunomodulating agents, such as interleukins and interferons. Biochemists disagree as to which molecules should be termed cytokines and which hormones. As we learn more about each, anatomic and structural distinctions between the two are fading.

chemokine = are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. Chemotaxis is simply the act of cells changing their movement according to certain chemicals in their environment.

lymphocyte = White blood cells. Large lymphocytes include natural killer cells (NK cells). Small lymphocytes consist of T cells and B cells.

macrophage = white blood cells which phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens.

granulocyte = a category of white blood cells characterized by the presence of granules (meaning "grains") in their cytoplasm (inside the cell membrane). These are thought of as the "phil" brothers of white blood cells: neutrophils, eosinophils, and basophils.

histopathology = the microscopic examination of tissue in order to study the manifestations or signs of disease.

vls = Gene locus in Borrelia burgdorferi which is required for encoding variable surface proteins.

vlsE = VlsE is a lipid-protein conjugate, found on the cell's outer surface during all Borrelia life stages. It is similar to a lipoprotein of the organism that causes African sleeping sickness. Unlike most proteins, VlsE is produced in many forms. It is a complicated protein with several variable regions (VRs), and six invariable regions (IRs).

When synthesizing VlsE, Borrelia periodically replace the VRs with new sequences. This replacement presents fresh surface antigens, and helps Borrelia remain invisible to the immune system. Within four days of being transferred to a mammalian host, VlsE will be produced with more than one VR suite, reducing the strength of the immune response. In ticks, VlsE does not modify the VRs. (Credit to Dr. Albert Burchsted, retired Field Biologist, for this description.)

antigenic variation = the mechanism in which an infectious organism alters its surface proteins in order to evade a host immune response. This change in antigenic profile may occur as the pathogen passes through a host population (also called "antigenic diversity") or may take place in the originally infected host.

The strategy is particularly important for organisms that a.) target long-lived hosts, b.) repeatedly infect a single host, and c.) are easily transmitted. Pathogens that express these characteristics and undergo antigenic variation have a selective advantage over their more genetically stable counterparts.

A number of bacteria use antigenic variation to evade the immune system, but Borrelia burgdorferi's method of antigenic variation is very complex and unusual compared to these.

In the case of Borrelia burgdorferi, the lp28-1 plasmid has been responsible for antigenic variation in vls locus - responsible for vlsE and the changing of Borrelia's outer surface proteins which helps it evade the immune system.

During the past decade, it was thought that removing the lp28-1 plasmid or altering its genetic material would remove Borrelia's infectivity entirely. It reduced it, but removing specific genes near the vlsE locus has done more to reduce Borrelia burgdorferi's infectivity.

The mutation of either of the genes encoding the two subunits of the RuvAB branch migrase blocked transfer of genetic information into vlsE during mouse infections, identifying the first required function for antigenic variation in the Lyme disease spirochete.

But basically, both the cis arrangement of vlsE and the vls silent cassettes in lp28-1 facilitate vlsE gene conversion.

See:
http://www.ncbi.nlm.nih.gov/pubmed/15501789
http://www.ncbi.nlm.nih.gov/pubmed/19266024
http://www.ncbi.nlm.nih.gov/pubmed/19997508

Source material:
The Linear Hairpin Replicons of Borrelia burgdorferi. Kerri Kobryn. Microbiol Monogr (7) Universite de Sherbooke, Sherbrooke, QC, Canada
Borrelia: Molecular Biology, Host Interaction and Pathogenesis.

complement = a small protein which mediates antibody response in the host's body. This is part of a complex immune system known as the complement system.

CRASPS = Borrelia produces complement regulator-acquiring surface proteins (CRASPs) that bind host complement factor H protein. Factor H protein is a negative regulator of the complement cascade (inactivates C3b). Borrelia produces a whole family of CRASP proteins. Different family members are able to interact with different factor H proteins from divergent hosts.

If that sounds too confusing, the thing to remember is that Borrelia has surface proteins which can bind to a host's complement's protein which then inactivates part of the complement system.

down-regulation = the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. (Up-regulation is the opposite process.)

So, as I've stated before - researchers do know that the infection can be persistent - the question and controversy has been over whether or not infection persists after one has antibiotic treatment. 

It's my opinion so far that it can persist - especially if one has neuroborreliosis and has been undertreated or untreated. Those who have been suffering from neuroborreliosis and reading this will say it definitely can persist, based on their experience. The question remains as to how one can know whether or not the infection has been eradicated. This is what needs to be known. 

Also, there is persisting, and then there is persisting... One of my nightmare scenarios has been that when the IDSA Lyme disease guidelines panel states that Lyme disease does not respond to long-term antibiotic treatments, what it really means that none of the antibiotics which exist today can effectively eradicate all of it and the immune system isn't always capable of mopping it up after antibiotic treatment.

This is why people began experimenting with a number of alternative treatments: in their experience and opinion, antibiotic treatment either failed to eradicate the infection or stop their symptoms - and sometimes the side effects or infection with C. difficile led to the decision to stop antibiotic treatment.

Onward...

Lyme Disease in Humans - from the last chapter in Borrelia:

"Lyme disease is a rapidly emerging tick-borne, complex, multi-system infectious disorder caused by the spirochetal bacterium Borrelia burgdorferi. The ailment, which affects adults and children alike, is widespread in the Northern Hemisphere and it continues to expand as humans encroach on the sylvatic habitat of the spirochete's mammalian reservoirs."

"Since first identified in the 1970s the incidence of Lyme disease has increased more than 30-fold and it is now considered the most prevalent arthropod-transmitted infection in both the United States and Europe."

This is why I say doctors should look at the possibility of ruling it in, more than ruling it out...

"B. burgdorferi is transmitted by ticks of the Ixodes ricinus complex, including I. scapularis, I. ricinus and I. persulcatus. In North America, B. burgdorferi sensu stricto is the only species proven to be pathogenic for humans [CO note: Relapsing fever Borrelia are pathogenic to humans too, and some species of Borrelia have yet to be determined for their pathogenicity in humans.]. In Europe, both B. afzelii and B. garinii are most commonly associated with human disease.

The spirochete's genomic features, as well as its unique molecular architecture, are considered to have a seminal role not only in how it is transmitted from ticks to humans, but also how it triggers immune responses in afflicted individuals. Inflammatory manifestations associated with the disease result from the host's innate and adaptive immune responses to the bacterium, rather than from toxigenic molecules, which borrelia cannot produce. Indeed, the deposition of spirochetes into human dermal tissue generates a local inflammatory response that becomes manifest as erythema migrans (EM), the hallmark skin lesion of Lyme disease in North America. In Europe, two additional dermatologic disorders, borrelial lymphocytoma and acrodermatitis chronicum atrophicans (ACA) are frequently associated with infection. EM is frequently accompanied by 'flu-like' symptoms, including myalgias, arthralgias and fever, which are generally believed to be cytokine-mediated in response to hematogenous spread of the bacterium. If treated appropriately, the prognosis is excellent; however, if untreated, patients may develop a wide range of inflammatory clinical manifestations, most commonly involving the central nervous system, joints and heart. Within days of treatment, the signs and symptoms associated with the disease typically begin to subside, although in some individuals a complete recovery can take several weeks or even months. A minority of treated patients may go on to develop a poorly defined fibromyalgia-like illness, which is not responsive to prolonged antimicrobial therapy. Below we integrate current knowledge regarding the ecological, epidemiological, microbiological and immunological facets of Lyme disease into a conceptual framework that sheds light on the disorder that healthcare providers encounter."

According to this, Borrelia burgdorferi does not produce toxigenic molecules, and most symptoms are believed to be cytokine-mediated in response to hematogenous spread of the bacterium. (hematogenous = originating in or spread by the blood). They are talking about all Borrelia there.

Hm. That's interesting. Does that mean that what people think is a Herxheimer reaction due to the release of toxins is actually something else, some other process?

I wanted to know what the deal is with this, so I looked it up... Huh, this was interesting:

Borrelia have abundant glycolipids but they do not have an endotoxin-like lipopolysaccharide. And the authors' running hypothesis is that the Herxheimer reaction is due to the action of lipoproteins on toll-like receptors (TLR2) in macrophages and other cells. Apparently, if you infuse antibodies that recognize TNFa (Tumor Necrosis Factor alpha) into someone who is infected with related Borrelia recurrentis before giving them penicillin, it reduced the severity of a Herxheimer reaction (Fekade et al, 1996 - full text at preceding link). When cytokine levels get quite high, this contributes to the reaction. (Borrelia, p. 339)

So, does this mean that detoxing is useless because there is no toxin to remove? The paper goes on to state that "...lipoproteins from two other spirochetes, B. burgdorferi and Treponema pallidum, induce the biosynthesis of tumor necrosis factor in murine macrophages."

So when patients are having a Herxheimer reaction, it is a reaction to the die-off induced by the immune system - not a reaction induced by a toxin.

Regarding the bit in the last section on persistence: Researchers are somewhat divided on this, and even as I write this, studies are published on the use of long-term antibiotic treatment for some of this minority of treated patients with persistent symptoms.

Dattwyler co-wrote this chapter along with Radolf, and one has to wonder if it would have been written somewhat differently and been left open to more uncertainty had Volkman or Barthold co-written it? Something to think about there.

At any rate...the running hypothesis is that infectivity of Borrelia species depends heavily on the evasion from the host response. And this evasion can be based on multiple mechanisms.

You've gotta just love the closing quote on the end of one chapter in the book...

Not.

“If our work with Borrelia has taught us one thing, it is to expect the unexpected. So we should not be surprised to discover that this phylogenetic ancient spirochaetal microorganism has developed several solutions of  its own and that it does not always conform to the dogmatic structure and function of the cell envelope of Gram-negative bacteria. We therefore anticipate a bright future with many challenges and unsolved mysteries for several generations of Borrelia researchers.”

Yeah. Right. Your science project is my life, man. I'm not looking at this as some professional subject of interest. My focus in this is different from yours. By a longshot, baby. By a longshot.

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17 Video: Shortcuts To Learning Immunology

I realize I posted a 14 part mini-series on Immunology not long ago and know that could be a bit much to bite off at once in order to learn more about the immune system.

So I've been spending time looking for shortcuts - ways for readers to quickly get up to speed on some of the terms and processes used when discussing the immune system.

I figure videos usually are the best way to begin learning for many people - so I have been watching them on Youtube to decide what to post here.

Let me just say that as entertaining as some of them are, I wish more of them were factually correct or just had more educational content in them.

I love the idea of using battle scenes from The Lord of the Rings movies as an analogy for the immune system - some creative guy did this, and it was hilarious. But most of it had no mention of the immune system or how it worked, beyond "the good guys are these immune cells, and the orcs are the invading pathogens". And then there was the guy who went so far as to make a 1950's style documentary on angry macrophages, with retro props and a fake ad for Solomon cigarettes... this documentary compared pathogens to invading Communists.

Unique. Original. Points for style. And yet, next to no substance.

What could have been both an entertaining and educational clip ended up an abysmal failure. C'mon guys, you can do better.


Anyway, I found what I hope are some of the better videos on Youtube that you can watch to learn more about the immune system, and the material on the first one will help you advance to the next video. Also, each video reinforces what you've seen in an earlier one - it helps familiarize you with the terms and concepts used.

Let me know if you have any trouble following these. For those of you who are already more advanced students of immunology and have gotten past all of this, I will be posting more intermediate and advanced videos on the immune system later. (Those who have watched these basic and intermediate videos first will be able to move on to the advanced section, which will mention toll-like receptors and interleukins.)

If you are a more advanced student and already understand those, then I would like to encourage you to comment more here and perhaps start your own blog to let people know more about the science of the immune system and infectious diseases like Lyme disease.

Knowing more about the immune system opens the door to understanding research out there done by the IDSA guidelines panel, scientific researchers in microbiology and molecular biology outside of the IDSA panel, the statements LLMDs have made about Lyme disease and its treatment, and claims other Lyme patients have made online.

Okay, without further delay, here are four videos which may prove useful for beginners - each under 10 minutes:

Immunology Overview [Time: 4:42] - overview of basic parts and terms of the immune system

The Immune System [Time: 9:36] - Basic explanation of the immune system and how it works.

Immune System, Part 1 [Time: 7:59] - Barriers and Non-Specific Defenses
Note that this video is accompanied by this easy to view PDF:
http://www.kirkwood.edu/pdf/uploaded/695/immune_and_lymphatic2.pdf

The Immune Response (Garland Science) [Time: 1:43]

That should be good to get you started.

Note that each one has slightly different information about the immune system, but the core material is the same. Being exposed to this information in different ways over time makes it easier to learn.

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0 Administrivia: Notes & Future Topics

Just popping in here for a moment amid fighting off some strange viral infection to leave a few short notes for my readers:

• When I'm feeling particularly unwell above and beyond my usual unwell, posting frequency may slow down. I'll try to give advance notice in comments or in a post like this one.
  
• Here's your notice: My posting frequency is slowing down now because I'm unwell.
  
• In general, new posts are less likely to be made during the weekend. What do I mean by "weekend" given everyone reading is in different time zones? Refer to island time.
  
• If I'm near a computer, I will check comments in the moderation queue during the weekend and post them.
  
• I may or may not respond to comments during weekends.
  
• Friday Four posts are sometimes posted as late as midnight Friday, Honolulu time (-10 h UTC/GMT).
  
• Reader comment & mailbag has included the following requests for further discussion: the immune system and how to build it, alternative medicine, XMRV, Morgellons, and the effectiveness of canine Borrelia blood tests.
  
• I plan to write an entry or two on each of these topics in the future. There is no guarantee on how soon each will be addressed. The timeline for each is dependent on my health, availability, other preexisting or newsworthy posts already in the pipeline, and the amount of time needed for additional reading and research to address each issue.
  
• Lymenet Europe has some interesting threads on Lyme disease organizations throughout Europe. I recommend viewing some of them, as well as guidelines different countries use. Tip: If you use the Chrome browser, you can translate web sites in other languages into English with a click of a button.

And now your moment of patient experience zen... This is something I think about when I get sick or am more symptomatic than usual - maybe some of you reading along will see yourself in it, too:

All I have to add for now. I'm going to lie down.

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0 Books: Mini Review on "Bull's Eye"

I've been reading bits and pieces from Bull's Eye: Unraveling The Medical Mystery Of Lyme Disease.

Someone told me it may be a frustrating read, so I was prepared for that - but it hasn't been that difficult to get through, actually, once you get past the fact that the author can write about Alan Steere more matter-of-factly than anyone I know.

That's one of the main criticisms I've heard other Lyme patients who have read it have about the book - but after reading a huge chunk of it, I'd have to say that it is more balanced about discussing the controversy than I thought it would be and that much of it focuses on things other than Steere: the history of Lyme disease in Connecticut, history of Borrelia in Europe, general research on Borrelia burgdorferi, epidemiology, difficulties in diagnosing Lyme disease, problems with serological testing, the Dearborn criteria, coinfections, shortcomings in the IDSA view of Lyme disease, the Ed Masters story, experimental treatments, genomes, vaccines, and legal issues.

And it's an easy read, for what it's worth - for the most part, people who aren't knowledgeable about Lyme disease or its controversy can jump right in and begin getting an idea of the big picture pretty quickly.

One of the things that makes it readable is the author, Jonathan Edlow, MD,  can outline procedures using metaphors and analogies in a basic way so that those reading this kind of material for the first time can 'get it', and I've found  the Ambiguity in the Lab chapter to be one of more interesting reads because of how it was written.

In the book, the author describes for the reader how Western blot tests are done for Lyme disease:

"Like the ELISA, the Western blot tests for antibodies, but it allows the laboratory to find precisely which antigens a patient's blood contains antibodies to - not just whether there are any kinds of anti-borrelial antibodies. 

First, the B. burgdorferi is put into a detergent to break up all its proteins. Each of these proteins has different sizes and each has a slight electrical charge. These proteins (antigens) are placed on a gel to which an electrical current is applied. The proteins then migrate across the gel, which is full of nooks and crannies, rather like an English muffin. Because the proteins have different sizes, they move through the gel at different rates, the larger ones moving more slowly than the smaller ones. After a certain amount of time migrating with the electrical current across the gel, the proteins from the B. burgdorferi have traveled different distances. 

Imagine a massive jungle gym with evenly spaced bars going every which way. A group of people who are four to seven feet tall are instructed to start at one end of the jungle gym and travel through the latticework as far as they can in five minutes toward the other side. In this group of people, ten are exactly four feet tall; ten are exactly four feet, six inches tall; ten are five feet tall, and so on - such that there are seven groups of ten people who are all the same height. 

Since the spaces between the bars of the jungle gym are uniform, the smaller people will be able to travel faster across this jungle than the larger, heavier people. When the five minutes are up, the larger people will be closer to the start and the smaller closer to the finish. Assuming that the participants are equal in their abilities, at the end of the five minutes, the seven groups will settle out in seven distinct regions of the jungle gym. If one were to take a picture of the apparatus at the end of the five minutes, it would show seven bands - clusters of people of the same height - interspersed with bare areas of the jungle gym devoid of anyone.

This is what happens to the proteins from borrelia in the Western blot. They migrate across the gel, through the network of obstructions, at different rates on the basis of their molecular weights. After a specified period of time, the proteins are clustered on the gel at specific regions. They are then transferred (blotted) onto a special kind of white membrane. Specific antibodies (attached to a dye and so that they can be seen) will bind to specific borrelial proteins, and colored bands will appear on the white membrane."

Edlow explains other processes and definitions by using metaphor and analogy throughout the book, making it easier to visualize them. He uses the idea of a machine to sort different kinds of fruit to explain what sensitivity and specificity mean in terms of blood tests detecting infection, and uses different models and makes of cars to help describe cross-reactivity in testing. The way he puts things makes it easier for people with no prior knowledge of Lyme disease and testing to understand certain concepts that they can later build on.

There are other reasons I like this book, and a few reasons I don't, but I wanted to take time aside to share this one aspect.

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

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

Dietrich Dorner, The Logic of Failure, 1988

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

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

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

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

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

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

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

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

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

Problems with Naming Conventions 

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

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

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

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

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

According to the IDSA, this means:

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

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

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

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

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

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

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

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

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

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

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

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

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

My Diagnosis of Different Names

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Documenting Chronic And Persistent Infection

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

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

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

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

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

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

The Patient's Dilemma

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

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

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

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

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

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

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

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

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

What About The Original Question?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

What does it take to confirm or challenge yours?

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

This work by Camp Other is licensed under a Creative Commons
Attribution-NonCommercial-ShareAlike 3.0 Unported License.

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