A Gold Standard?

 

Gold Standard Diagnostics’ Next-Generation Lyme Disease Testing Becoming Widely Accepted Amongst Clinical Laboratories.

June 19, 2013

DAVIS, Calif. -- Gold Standard Diagnostics, Corp. (GSD, www.gsdx.us), a leading manufacturer and marketer of clinical laboratory instrumentation and assays for the in vitro diagnostics market, announces new Line Immunoassay technology for Lyme confirmation testing. GSD gives clinical laboratories an FDA cleared, improved option for serological confirmation testing for Lyme disease according to the CDC-recommended two-step process. Both the IgG and IgM line blots are substantially equivalent to traditional Western Blot technology, but offer advancements in usability and objectivity through use of Line Immunoassay technology. GSD’s LIA test strips offer numerous enhancements including: improved sensitivity and specificity, consistent results, large lot sizes, easier handling and automation options.

“The demands of today’s clinical laboratories require consistent, reliable and user-friendly products said,” John Griffiths, CEO of Gold Standard Diagnostics. Gold Standard’s innovative quality products, automation options, and excellent service meet those needs. The advanced technology of the GSD Lyme LIA can improve test results, workflow efficiency and cost effectiveness for these clinical laboratories.”

Who's Watching BioWatch?

BioWatch [previously mentioned here and here] faces congressional hearing this week. A House panel will question officials under oath about the troubled system designed to detect airborne releases of anthrax or other biological weapons.

June 16, 2013|By David Willman, Los Angeles Times

WASHINGTON — A decade ago, then-Homeland Security Secretary Tom Ridge oversaw the start of BioWatch, the nationwide system designed to detect airborne releases of anthrax or other biological weapons.

In his 2003 State of the Union address, President George W. Bush had announced that BioWatch would "protect our people and our homeland."

"Everyone knew it was a primitive, labor-intensive, fairly unsophisticated attempt," Ridge recalled in a recent interview.

On Tuesday, a congressional panel is scheduled to question officials publicly about the program under oath. The House Energy and Commerce Committee began examining BioWatch last year in response to reports in the Los Angeles Times about the system's deficiencies.

In more than 30 U.S. cities, BioWatch units on rooftops and other outdoor locations suck air through dry filters, which are removed every 24 hours and tested at public health laboratories. BioWatch samplers have also been deployed at major spectator events, including the Super Bowl and national political conventions.

The system has been beset by false alarms — nearly 150 to date — some of which triggered tense deliberations over whether to order evacuations, distribute emergency medicines or shut down public venues. In each case, authorities decided to disregard BioWatch.

Confidential government tests and computer modeling have pointed out an even more serious failing: BioWatch could not be relied on to detect an actual germ attack, according to people familiar with its operations.

The federal government has spent more than $1 billion on BioWatch, and the Obama administration has taken preliminary steps to spend billions more on an automated "Generation 3," in which air samples would be continuously analyzed by a "lab in a box" within each unit.

Deployment of Generation 3, however, has stalled. In March, members of the House and Senate appropriations committees — citing "serious concerns" about Generation 3 — said they were declining the Obama administration's request for nearly $40 million for further testing and evaluation of the technology.

The committees reiterated their request that — before a final contract is awarded for the automated system — Homeland Security Secretary Janet Napolitano "certify … that the science used to develop the technology is proven."

Napolitano's subordinates have repeatedly played down or denied flaws in the existing system.

Last year, the department's chief medical officer, Dr. Alexander Garza, a presidential appointee, asserted that BioWatch had never generated a "false positive."

Most of BioWatch's false alarms were triggered by organisms that are genetically similar to lethal pathogens but pose no threat to humans, according to people knowledgeable about the system.

Garza maintained these were not false positives because BioWatch found something in the environment, albeit not the deadly microbes it was intended to detect.

Experts appointed by the National Academy of Sciences have rejected this viewpoint — concluding in a 2010 report that all misidentifications of a pathogen by BioWatch were false positives that "signaled the potential occurrence of a terrorist attack when none has occurred."

The House investigative panel said in a statement last week that BioWatch "has been plagued by false alarms and other failures." According to information newly verified by federal officials, BioWatch has generated at least 149 false alarms.

Garza resigned his post this year to accept a private-sector job. Congressional investigators have questioned others at the Homeland Security Department and the U.S. Centers for Disease Control and Prevention, which administers the nation's stockpile of medicines to treat those exposed to a germ attack.

The investigators have sought to learn why Homeland Security Department officials did not do more to avert false detections of the bacterium tularemia after BioWatch's first false alarms for it in late 2003. Tularemia, also known as rabbit fever, can infect and in rare instances kill humans at relatively low concentrations.

In addition to pressing officials about BioWatch's troubles, investigators have traced how the system functions on a daily basis.

In the event of an intentional release of a pathogen, 36 hours or more could pass before lab testing of BioWatch filters alerted officials to the attack. By then, victims might be crowding emergency rooms, undermining the notion that BioWatch would allow authorities to quickly safeguard a stricken area or dispense medications in time to prevent sickness or death.

BioWatch was installed in 2003 amid widespread fear of biological terrorism — fear stoked, Ridge said, by the fall 2001 anthrax letter attacks, which killed five people.

The FBI ultimately traced those attacks not to a foreign terrorist but to a U.S. government scientist, Bruce E. Ivins, based at the Army's biowarfare research center at Ft. Detrick, Md. Ivins committed suicide in July 2008 after learning that prosecutors were preparing to file charges against him.

Given BioWatch's performance, Ridge said his former department should be wary of sinking more money into it. BioWatch, he said, evokes the Homeland Security Department's $1-billion attempt — now abandoned — to use experimental technology as an invisible fence along the U.S.-Mexico border.

"What [Homeland Security] cannot afford to have if it's going to sustain any credibility with the public is the same kind of thing they did along the border," Ridge said.

The Mouth That Bored. Again. And Again. And Again.

The LYME POLICY WONK blog is written by Lorraine Johnson, JD, MBA, who is the Chief Executive Officer of LymeDisease.org.

Dr. Lyle Petersen of the CDC wrote an editorial for the Poughkeepsie Journal in response to the remarkable series of articles by Mary Beth Pfeiffer on Lyme Disease. In his letter, Dr. Petersen restates the IDSA/CDC perspective patients have long heard. Lyme disease is easy to diagnose and treat, but for those with chronic Lyme treatment is both ineffective and dangerous. He proposed that we work on preventing Lyme disease and early diagnosis and treatment—both laudable goals, but not at the expense of treating seriously ill patients. My response to his letter, which I posted on the Poughkeepsie website (and encourage you to respond there as well) follows.

Response to Dr. Petersen:

Let me try to reframe the issue for Dr. Petersen and the CDC, which seems to have lost its way in patient care.  We have a growing health crises. More patients are becoming ill every year. These patients are very sick—and suffer a quality of life equal to that of patients with congestive heart failure.  Our survey of over 4,000, published in Health Policy, found 65% had had to cut back on or quit work or school at some point; 28% for more than one year.

[There’s that Klempner comment about congestive heart failure from a dozen years ago.  The Lymees like to use it, but they always fail to mention that it refers not to so-called “chronic” Lyme patients in general but rather to the handful of people (129) who enrolled in a treatment trial for persistent Lyme symptoms.  Lorraine’s surveys (previously noted here) of self-selected people who think they have a permanent Lyme infection are meaningless given the self-selected participants and the crudely phrased, leading questions. These are the same people who are allegedly too sick to work and too poor to afford treatment.  Yet, they fly or drive off to protests and rallies, wearing their lime green t-shirts, waving their lime green placards, giving speeches, handing out propaganda, and snapping photos of each other waving and smiling for posting on Facebook and Flickr.  There’s a disconnect between activists’ answers to fake surveys and the photographic evidence they post online.] 

I am not sure what Dr. Petersen means when he says patients only have anecdotal evidence. Does he mean that the studies by Oksi, Donta, Cameron, Fallon and Krupp showing patient improvement do not exist when he is the one picking and interpreting the evidence?  Yes, those last two are NIH funded trials that the CDC has chosen to interpret in a manner that harms patients and denies them care. 

[Those treatment trials have been discussed previously here and here and here.  Lyme activists have been trying to discredit or simply ignore the results of these studies for years.]

No one doubts that we have not yet determined the optimal treatment for Lyme patients.  The fact is that those charged with our public health are not even trying.  Our large scale patient surveys show that short term treatment fails for over 90% of patients with chronic Lyme. I must think that Dr. Peterson’s jests when he says treatment must be based on the best research—what he is saying is that there should be no treatment and no research for treatment. This “do nothing” response denies patients access to the only treatment option available to them that has any efficacy and that has given many patients back their lives. For seriously ill patients, “waiting” is not an option.

[That’s a lot of hysteria and bullshit in one paragraph. Again, her surveys of treatment failures in self-selected “chronic” Lyme patients are meaningless for reasons stated above, and because the activists have no clear definition of what “chronic” Lyme is suppose to be, and because most of them probably never had Lyme borreliosis to begin with so antibiotic treatment would not likely have an impact on whatever their true health problems are.  For persons with an actual Lyme infection, there are efficacious antibiotic treatments with high cure rates.] 

 It’s no wonder then that more than 85% of patients with chronic Lyme have little to no trust in the IDSA guidelines.  It’s no wonder that the CDC is suffering a crisis of credibility with patients.  Decision making by those who aren’t impacted, and who are not accountable to patients is what has got us into this crises.  The only road back must involve public policy making that includes representation of all stakeholders—not simply those of a single special interest group with a vested interest in maintaining its lock on research grants.  Patients and treating physicians need to have a voice in public policy decisions that impact their lives so profoundly.

[There will never be any trust among Lyme activists, many of whom believe the government is involved in biological warfare experiments against them and that Nazi doctors were working on tick-borne diseases on Plum Island, New York until said diseases and ticks escaped and magically appeared in Old Lyme, Ct.  It’s hard to have a calm and rational dialogue with people who are wearing tinfoil hats and who think you are trying to kill them.  Lawyer Lorraine doesn’t do much to quell that paranoia with her own wild accusations about “a single special interest group with a vested interest in maintaining its lock on research grants”.  Lyme patients and their quack doctors may be entitled to a voice in public policies, but they are not entitled to ignore psychologically- and financially-inconvenient facts or to cherry-pick bits of evidence-based medicine.]

Americans and Europeans Really Are Different

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Li X, Strle K, Wang P, Acosta DI, McHugh GA, Sikand N, Strle F, Steere AC. Tick-Specific Borrelial Antigens Appear to Be Up-Regulated in American but Not European Patients with Lyme Arthritis, a Late Manifestation of Lyme Borreliosis. J Infect Dis. 2013 Jun 12.

There are several possible explanations for antibody responses to tick-specific Bb antigens in LB. First, we have previously shown that antibody responses to OspA and OspB, which are closely related proteins, are the last to develop, suggesting that spirochetes may express these proteins only after prolonged infection. However, in the current study, European patients with ACA, which also occurs months to years after the onset of infection, rarely had antibody responses to these tick-specific antigens, implying that it is not simply the duration of the infection that leads to spirochetal expression of these proteins. Since American patients in our study were almost exclusively of European heritage, it is likely that genetic variations in spirochetes, rather than host factors, account for these differences in antibody reactivity.

In its enzootic life cycle, the spirochete up-regulates OspA when preparing for entry into an engorging tick. The host neuroendocrine stress hormones, epinephrine and norepinephrine, may play a role in stimulating OspA expression during tick feeding. However, this mechanism would not explain why OspA antibody responses in humans are found almost exclusively in American LA patients. Rather, we think that the marked joint inflammation associated with Bb infection in the northeastern US is likely to be the major reason for de-repression of OspA. Zymosan, a potent inflammatory reagent, induces OspA expression in Bb spirochetes cultivated in dialysis membrane chambers implanted in mouse peritoneal cavity. Moreover, cell culture studies have shown that Bb strains from the northeastern US have greater inflammatory potential than Ba or Bg strains from Europe.

There may be also mechanistic differences in production of antibodies to OspA and BicA in American LA patients. Over the 30-year period during which serum samples were collected, there was a significant increase in antibody responses to BicA after the introduction of antibiotictherapy for the treatment of LA in 1983, which was not the case with the responses to Bb lysates or OspA. Thus, antibody to OspA, an outer-membrane lipoprotein, was found both in antibiotic-treated and non-antibiotic-treated LA patients, whereas BicA, an intracellular metal-binding protein, was found primarily in antibiotic-treated patients. Perhaps antibiotic-mediated killing of spirochetes helps expose cytosolic BicA to host immune recognition. Therefore, while marked inflammation may de-repress OspA and BicA, antibiotic treatment seems to be important in further stimulating BicA antibody response.

In summary, American LA patients from the northeastern US often had robust antibody responses not only to OspA, but also to other tick-specific Bb proteins. In contrast, these responses were rarely found in patients with early manifestations of the infection, and low-levelresponses to these proteins were observed in only a few European patients with late manifestations of the disease. We hypothesize that it is primarily differences in the spirochetes that lead to up-regulation of the tick-transcriptome in LA patients in the northeastern US. Uncovering the genetic elements in spirochetes that lead to these responses will be important in helping to understand why Bb genotypes in the northeastern US are particularly arthritogenic.

Bad Stats, Bad Conclusions, Bad Investigators

Notes from:

Treatment Trials for Post-Lyme Disease Symptoms Revisited.  Mark S. Klempner, Phillip J. Baker, Eugene D. Shapiro, Adriana Marques, Raymond J. Dattwyler, John J. Halperin, Gary P. Wormser.  Am. J. Med. 2013.

Delong et al. present their analyses as a rigorous, independent evaluation of the results of the reported clinical trials, they are based on questionable assumptions, and the authors fail to disclose their support of long-term treatment with antibiotics and alternative treatments for Lyme

disease.

Delong et al state that posttreatment symptoms of Lyme disease are of the same severity as those of multiple sclerosis or congestive heart failure, based on the severity of the symptoms of some patients in the trials.

…the patient populations in the studies purposely comprised only individuals with severe symptoms rather than with the full spectrum of post-Lyme disease symptoms.

The lack of credible evidence for Lyme disease is one of the reasons that recruitment of subjects was so difficult in all of the trials.  At least 40% were excluded because of lack of documentation of previous Lyme disease.

Delong et al seem to have a fundamental misunderstanding of the effects of antibiotic therapy in active infections (acute, subacute, or chronic), which are far from subtle.

…it would be expected that a lower standard for improvement also would result in a larger number of patients with improvement in the placebo-treated group; this would further diminish any difference between the groups and make a different result extremely unlikely.

At 1 month, the reduction in fatigue among placebo recipients was even greater, and the results were indistinguishable from those in the antibiotic-treated group.

Delong et al failed to mention that in the study by Krupp et al, one third of the placebo recipients did not complete the study as originally designed.

Thus, fatigue as measured by this scale can decline by as much as 15% among placebo recipients with post-treatment symptoms of Lyme disease.

Delong et al also failed to mention other important issues related to the Krupp et al trial. The study by Krupp et al hypothesized that fatigue was due to residual Borrelia burgdorferi infection of the central nervous system specifically. This was so fundamental to the rationale for their study that they designated 3 co-primary end points, improvement of fatigue along with both cognitive improvement and clearance of a borrelial antigen from cerebrospinal fluid. Delong et al try to discount the lack of cognitive improvement in the study by Krupp et al, emphasizing that cognitive impairment was not an entry criterion….

Contrary to the assertions of Delong et al, on the basis of this assessment of fatigue there was no benefit from 10 weeks of intravenous ceftriaxone in the study by Fallon et al. In their post hoc analysis, a reduction of 0.7 points in the fatigue score was observed in 66.7% of ceftriaxone-treated patients versus 25% of placebo-treated patients. Fallon et al cite a P value of .05; this is misleading, not only because it is a post hoc analysis but also because no statistical correction was made for the multiple post hoc comparisons that were performed by the authors.

Delong et al also failed to mention contradictions between the study by Krupp et al and the study by Fallon et al.

Delong at al mention that the study by Fallon et al found, among the secondary outcomes, that patients with worse baseline pain and physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24. The validity of this post hoc analysis also is questionable, and not simply because it was post hoc. 

All of the patients enrolled in the 4 retreatment studies of patients with post-treatment symptoms of Lyme disease had already been treated for Lyme disease, often with extensive courses of antibiotics.  Thus, it is hardly surprising that neither microbiologic nor molecular evidence for residual infection was found at any site in any of the 4 trials.

A consistent observation has been that patients with long-term subjective symptoms after treatment do not eventually develop an objective late clinical manifestation of Lyme disease, such as Lyme arthritis.

Patients with objective evidence of treatment failure are rare with currently recommended antibiotic regimens, but this can occur.

Moreover, to justify intensive retreatment with antibiotics, an additional criterion needs to be met—that retreatment both resolves the infection and relieves the symptoms. Those who argue that antibiotics cannot fully eradicate Borrelia burgdorferi from animals or patients never provide evidence for why, if this were true, longer courses of antibiotic therapy would overcome this limitation.

CONCLUSIONS

Delong et al fail to provide credible or convincing evidence that the methodology, findings, and conclusions of the study by Klempner et al1 are invalid or that the other National Institutes of Health-sponsored retreatment trials show any evidence that post-treatment symptoms of Lyme disease are due to persistent infection. Neither of the analyses provided by Delong et al or Fallon et al justify a conclusion that there is a meaningful clinical benefit to be gained from retreatment with parenteral antibiotic therapy.

Much worse than Lyme

A 6-year-old North Carolina girl has died from Rocky Mountain spotted fever, a bacterial infection transmitted by ticks.

Emilee Russell of Black Mountain, N.C., died Wednesday, two-and-a-half weeks after she was bitten by a tick over Memorial Day weekend, ABC affiliate WLOS reported. Her family was visiting relatives in Texas at the time of the tick bite.

The American dog tick is the most common source of R. rickettsii, the bacterium behind Rocky Mountain spotted fever, according to the U.S. Centers for Disease Control and Prevention. The infection is rare in Texas, affecting one in 1 million people, according to 2010 CDC data, whereas North Carolina has one of the highest rates in the country, with up to 63 cases per 1 million people.

Symptoms of the infection include fever, headache, vomiting, abdominal and muscle pain, and sometimes a rash, according to the CDC.

“Rocky Mountain spotted fever can be severe or even fatal if not treated in the first few days of symptoms,” the agency says on its website. “Patients who are treated early may recover quickly on outpatient medication, while those who experience a more severe course may require intravenous antibiotics, prolonged hospitalization or intensive care.”

What did nutty people do before the Internet?

From the online forum at LymeNet.  This is why Lyme disease activists are often referred to as LymeNuts.  Emphasis on “nut.”

06-14-2013

I realise the above is not very clear. I am under stress at the moment, so I apologise.

What I am saying essentially is this -

1 The US and NATO defence departments are behind the Lyme coverup. The insurance, patents and other financial conflicts of interest of the Denialists are important too, but they are SECONDARY to what is going on.

Anyone who starts to understand this finds themselves immediately contacted by people working with the Tea Party in the US, and other racist and fascist political parties, who try to distort the whole issue by linking it to stupid racist conspiracy theories, or ridiculous tales of lizards or aliens or zombies somehow controlling the US army.

Thus Lyme activist and biochemist Kathleen Dickson discovered important and valid information re the dangers of the Lymerix vaccine and other scientific data re Borrelia infection implicating the Denialists in fraud.

She was immediately persecuted by McSweegan and other denialists, but also AT THE SAME TIME - targeted for major brainwashing by American neonazis,to discredit her. Now they have won her to their cause and her valid scientific findings are lost amongst a sea of nonsense such as "Bush' Jewish Communists were behind the Boston marathon Bombing" and other nonsense.

In UK David Icke is pushing the same nonsense and is being massively funded to launch a new media initiative with sonia Poulton, Daily Mail journalist.

Jerry Leonard has a controller by the name of Gergory Gaines. Gaines is a CIA officer involved in defence-related industry, as is Jerry Leonard, esp Scitor and TriQuist. It was after I learned this last night that the surveillance and harassment against me was taken to a new level.

As for Lady Mar, the email I was referring to is a private email she sent to me, and others. I have not named the other recipients for their protection. Hard copies of the email are in safekeeping, in more than one country.

In the past Lady Mar was willing to raise the biowar issue. She asked a question in parliament re Lyme being studied at Porton Down as a bioweapon, and received an evasive answer. She asked the question at my request and it is archived in Hansard which records all parliamentary business in the UK.

Since her trip to Porton she will no longer raise these issues and wants the rest of us to stop as well.

[earlier in this delusion….]

I tried to post important info to http://biotech.indymedia.org/ as the Indymedia site refuses to use US govt technology which enables a back-door control and censorship. In the past I have been able to post information using that route. But now as far as I can see the site is down.

The gist of my post was as follows:

I have been subject to persecution for some years now because I research and write about the Lyme-biowarfare link.

Certain individuals from the neo-fascist movement and the American Tea Party, who are equally vocal about that link, but distort the information by mixing it in with absurd conspiracies about lizards from outer space, secret Jewish conspiracies, racism against non-whites etc do not suffer the persecution that I and others have suffered.

Why?
I found out last night but immediately following this virtually every one I talk to on the phone can no longer use their phones.

I am not referring to Lyme activists, but just ordinary people in my life to do with work etc, and friends who have nothing whatsoever to do with my Lyme activities.

I am now deeply concerned for the safety of my family.

In my Indymedia post I referred to a CIA officer called Gregory Gaines, to the Scitor and TriQuint defence contractors, to Jerry Leonard in the US and David Icke in the UK, and also to an email received by me and others from Lady Margaret Mar, the countess of Mar. I did not name my co-recipients for their protection.

The gist of the email was as follows:

The British biowarfare establishment knows that we know the truth re Borreliosis, but they will never admit it because of the Official Secrets Act, so please can we shut up about it all, and perhaps they will help Lyme patients.

Lady Mar, you are wrong. They will not help the millions of victims of their evil coverup.

They have had forty long years to help us if they wanted to. They did not then and they will not now.

We will only get help when we expose this. Any one of them could whistle-blow if they wanted to - Nuremberg laws mean that being ordered to do something because of your govt's military (ie the Official Secrets Act), does not take precedence over your duty to ethics and to humanity.

That is why I did not shut up.

Elena Cook

[Don’t forget to adjust your tinfoil hats before going outside.]

It’s Not Quite the March of Dimes Approach

Here’s a note from the Lyme activists in California:

How the Lyme community stepped up--with donations big and small--to buy a sophisticated microscope and support the groundbreaking research of Dr. Eva Sapi.

More than 20 years of government-funded Lyme disease research hasn’t brought us any closer to a cure.

[Actually, it’s more like 30+ years of funded research.  As for a cure, well it’s the same cure as with any other bacterial infection:  antibiotics.  Eight dollars worth of doxycycline usually does the trick.]

Basically, the same folks who created the IDSA Lyme guidelines–which systematically deny care to thousands of Lyme patients every year–also have a lock on government-funded Lyme research money. This results in dead-end projects that waste time and money and do nothing to help suffering Lyme patients.

[Interesting.  So 14 people—two of who are from Austria and Slovenia and therefore would have a hard time getting US funds—have a lock on federal research dollars.  Maybe if we type “lyme” or “borrelia” into the NIH research database we can just check that alleged “fact.”]

That’s why we support the trailblazing Lyme research of Dr. Eva Sapi, of the University of New Haven. She has made great strides towards solving the puzzle of Lyme disease—developing new culture techniques, investigating how antibiotics affect all forms of the Lyme bacteria, and examining the role of biofilms in Lyme. She is committed to finding out why the Lyme bacteria can persist in the face of antibiotic treatment, which is critical to finding a cure.

[Trailblazing?  Sorry, never heard of her.  I assume she’s another lone genius struggling against the vast indifference and incompetence of two generations of well-regarded and well-funded I.D. experts and scientists.  Or is it because she herself is a “Lyme victim” and an advocate for chronic Lyme disease, and tells her fellow victims exactly what they what to hear?]

A few months ago, we found out she needed a new piece of equipment–an atomic force microscope–to take her research to the next level. This sophisticated instrument can magnify the Lyme spirochete 1000 times more than standard microscopes, allowing her to observe many live forms of Borrelia under many different conditions. One of these babies costs about $110,000. We contacted some of our donors privately, asking if they wanted to help out. Some generous people answered that call, and by April,  we needed only $20,000 more to complete the purchase.

[Interesting approach.  Yet, it’s in keeping with this kind of antiscience activism.  A 2011 piece in Lancet I.D. noted the following: “As with other antiscience groups, some Lyme disease activists have created a parallel universe of pseudoscientific practitioners, research, publications, and meetings….”** Two separate and distinct universes with different experts, outcomes, beliefs, etc.  And if I remember my theoretical physics, there can be no communication between those separate universes.  Still, echoes of staged protests, accusations of corruption and conspiracy, harassment and death threats, and orchestrated legislation to subvert evidence-based medicine and peer-reviewed science do seem to seep through on occasion, but it’s a sporadic, one-way transference.]

Subtle Spirochetes through the Ages

Zückert WR. A Call to Order at the Spirochetal Host-Pathogen Interface. Mol Microbiol. 2013 Jun 10.

Spirochetal infections have had and continue to have a significant impact on human morbitity. The global spread of syphilis likely started in the 15th century when ships returning from the newly discovered Americas introduced Treponema pallidum to a thus far naïve European population and wasn’t effectively controlled until the general availability of penicillin in the 1940s. Some evidence suggests that leptospirosis and its agent Leptospira interrogans crossed the Atlantic in the other direction and may have shaped the history of early European settlements, only to become the most common zoonotic disease worldwide. Similarly, clinical descriptions from the 1880s and molecular evidence from more than 5000-year-old tissue samples indicate that Borrelia burgdorferi was present in Europe long before re-emerging as the cause of an infectious syndrome on the East Coast of the United States in the 1970s; Lyme borreliosis today is the most common vector-borne infection in temperate climates of the Northern hemisphere.

The Machiavellian ambition and triumph of these three spirochetal agents probably best articulates itself in their common propensity to cause persistent infection, particularly in reservoir hosts that are able to efficiently spread the disease. With the exception of syphilis, humans are considered incidental, “dead-end” hosts that will not facilitate transmission of the disease but nevertheless suffer from the consequences of an untreated infection. The mechanisms that allow B. burgdorferi to persevere inside the natural tick-vertebrate transmission cycle as well as during human infection have been the focus of a large number of studies. The bacterium’s major persistence traits can be classified under three categories.

First – and common to all spirochetes – is the high degree of motility that enables the slender bacteria to penetrate and disseminate in host tissues. Cases in point for motility’s importance in the transmission cycle of B. burgdorferi are that mutants in the major B. burgdorferi periplasmic flagellar protein FlaB, which lack the typical flat-wave motility, show reduced viability inside the tick and are unable to establish infection in an immunocompetent mouse model of infection.

The second and third categories, adhesion and immune evasion, both involve processes occurring at the host-pathogen interface. On the B. burgdorferi side, this interface is dominated by a large and diverse set of peripherally membrane-anchored surface lipoproteins. It therefore may not be surprising that an ever-increasing number of surface lipoproteins have been shown to bind host factors such as extracellular matrix components (e.g., fibronectin, proteoglycans, collagen or laminin), protease precursors (plasminogen), or complement regulatory factors (e.g., factor H).

…this study (Molecular Microbiology, Tilly, Bestor and Rosa, 2013)** proves that extracting the secrets from a pathogen that has honed its ways through eons of evolution sometimes may require subtle tools that minimally disrupt subtle and sometimes covert mechanisms. The Borrelia surface has been metaphorically likened to a “rainforest,” where lipoproteins may form different layers of the canopy. Introduced overrepresentation of some of them may sufficiently disturb interactions within the surface proteome to have unintended consequences like the shielding or exposure of other virulence factors at the host pathogen interface.

**Mol Microbiol. 2013 May 22. Lipoprotein succession in Borrelia burgdorferi: similar but distinct roles for OspC and VlsE at different stages of mammalian infection. Tilly K, Bestor A, Rosa PA.

Borrelia burgdorferi alternates between ticks and mammals, requiring variable gene expression and protein production to adapt to these diverse niches. These adaptations include shifting among the major outer surface lipoproteins OspA, OspC, and VlsE at different stages of the infectious cycle. We hypothesize that these proteins carry out a basic but essential function, and that OspC and VlsE fulfil this requirement during early and persistent stages of mammalian infection respectively. Previous work by other investigators suggested that several B. burgdorferi lipoproteins, including OspA and VlsE, could substitute for OspC at the initial stage of mouse infection, when OspC is transiently but absolutely required. In this study, we assessed whether vlsE and ospA could restore infectivity to an ospC mutant, and found that neither gene product effectively compensated for the absence of OspC during early infection. In contrast, we determined that OspC production was required by B. burgdorferi throughout SCID mouse infection if the vlsE gene were absent.

Together, these results indicate that OspC can substitute for VlsE when antigenic variation is unnecessary, but that these two abundant lipoproteins are optimized for their related but specific roles during early and persistent mammalian infection by B. burgdorferi.

A Radical Idea: Guidelines

NYT, June 11, 2013

Healing the Overwhelmed Physician

By JERRY AVORN

BOSTON — DURING an 1817 visit to Florence, the French author Marie-Henri Beyle, known by the pen name Stendhal, was seized by palpitations, dizziness and a feeling of being overwhelmed by the abundance of great art surrounding him; an Italian psychiatrist later coined the term Stendhal syndrome to describe this phenomenon.

We physicians are susceptible to a kind of medical Stendhal syndrome as we confront the voluminous evidence about the clinical choices we face every day. It would take dozens of hours each week for a conscientious primary care doctor to read everything he or she needed in order to stay current — a dizzying and impractical prospect.

To remedy the problem, many medical groups issue clinical-practice guidelines: experts in a field sort through the reams of clinical research on a medical condition and pore over drug studies, then publish summaries about what treatments work best so that physicians everywhere can offer the most appropriate, up-to-date care to their patients.

Read the entire article at the New York Times.

Maybe a high school course in Prbabaility and Statistics would help

From the Atlantic Monthly.
The Irrationality of Giving Up This Much Liberty to Fight Terror.
When confronted by far deadlier threats, Americans are much less willing to cede freedom and privacy.
Conor Friedersdorf
Jun 10 2013.

Latest Political Attacks on IDSA Guidelines for LD Treatment

Anti-science politicians continue to attack the Infectious Diseases Society of America on behalf of Lyme disease activists and their for-profit physicians.  The latest attempts at political intimidation are reported (and encouraged) in the pages of the pro-activist newspaper, the Poughkeepsie Journal. 

Lawmakers question Lyme treatment guidelines

Poughkeepsie Journal

June 9, 2013

A U.S. senator and three House of Representatives members are demanding to know why 7-year-old treatment guidelines for Lyme disease were not revised under rules that require updating every five years — rules guideline managers say don’t apply.  In a May 17 letter, U.S. Sen. Richard Blumenthal, D-Conn.; and U.S. Reps. Chris Gibson, R-Kinderhook, Chris Smith, R-N.J., and Frank Wolf, R-Va., said Lyme disease treatment guidelines did not undergo a “thorough review process” before they were re-posted in 2010 on a federal website called the National Guidelines Clearinghouse.

Spokespersons for the Infectious Diseases Society of America, which authored the treatment protocols, and the Guidelines Clearinghouse said the guidelines met standards for posting because they were reviewed in 2009 in settlement of a threatened antitrust action. At the time, Blumenthal, then Connecticut’s attorney general, had charged that the disease society authors had conflicts of interest that biased them against evidence of “chronic” Lyme disease. The disease society agreed to have a separate panel of experts review the guidelines, which were upheld.

[snip]

But Diana Olson, spokeswoman for the Infectious Diseases Society, said a review is performed every 12 to 18 months, with the society “currently in the process of determining whether the Lyme disease guideline needs to be updated, based on evolving science.” She defended the work of the 2009 guidelines panel, which she called “a comprehensive review.”

The new letter from Blumenthal and the three House members challenges the guidelines by maintaining the panel was specifically “not charged with updating or rewriting” the guidelines as part of the settlement; they asked federal officials to explain the decision to maintain the guidelines, which will have been posted for nine years by the time they expire.

The letter is the latest in a series of attempts to undermine the ironclad guidelines, which attribute most lingering symptoms of Lyme disease “to the aches and pains of daily living,” angering people who believe they suffer chronic infections.

[snip]

In explaining their latest inquiry, the legislators said they “often hear from our constituents about the severe consequences of this disease and the unnecessary hurdles to care faced by those who are suffering with Lyme. Unfortunately, insurance companies continue to deny Lyme disease treatments on the basis of the … guidelines,” stated the letter, which was released by Gibson.

While allowing the 2006 Lyme guidelines to stay in place though they would ordinarily have expired in 2011, the National Guidelines Clearinghouse removed competing guidelines of the International Lyme and Associated Diseases Society when they expired in 2010. A clearinghouse official said the society had failed to update them.

“The organization was not able to produce documented evidence that the guidelines were reviewed or revised within the five-year period,” said Alison Hunt, a spokeswoman for the Agency for Healthcare Research and Quality, which manages the clearinghouse.

The Infectious Diseases Society met the requirement by virtue of the 2010 panel report, she said. Olson asserted the guidelines have withstood scrutiny. “The panel concluded that all of the recommendations were supported by the best available evidence,” she said, noting the group — “vetted by an impartial ombudsman for any potential conflicts of interest” — considered all information, evidence and “points of view.”

[snip]

This is just the latest effort to attack and undermine the evidence-based guidelines of the IDSA.  Activists’ antics about the guidelines and the coerced review engineered by Blumenthal have been reported in numerous posts here since 2009.  

IDSA guidelines are in keeping with similar practices and recommendations in the U.K. and the E.U.  Yet, no health organization or society outside the U.S. recommends using the ILADS guidelines.  In a Jan. 13, 2011 post I noted:

At the request of the Chief Executiveof the Health Protection Agency (HPA) an independent working group chaired by Professor Brian Duerden CBE, Inspector of Microbiology and Infection Control, Department of Health, reviewed the International Lyme and Associated Diseases Society’s (ILADS) “Evidence-based guidelines for the management of Lyme disease” (Cameron et al. Exp Rev Anti- infect Ther 2004;2:S1-13).  “The ILADS guidelines are poorly constructed and do not provide a scientifically sound evidence-based approach to the diagnosis and care of patients with Lyme borreliosis.”

Similarly, a Dec. 6, 2012 post about a Norwegian review of Lyme disease noted:

“The ILADS guidelines match the view of most Lyme patient support groups, several web sites, and also the coverage of chronic Lyme in media, while the IDSA, EFNS, and updated EUCALB guidelines represent the view of so-called evidence-based medicine. We do not support the ILADS guidelines as there is an accumulating body of evidences against persistent ongoing Bb infection in patients with non-specific symptoms without objective clinical findings and laboratory support. These evidences encompass carefully conducted laboratory studies and controlled treatment trials, most of them summarized in a much cited review article published by an Ad Hoc International Lyme disease group in 2007, but also emphasized in other reports. (Ljøstad U, Mygland A.  Chronic Lyme; diagnostic and therapeutic challenges.  Acta Neurol Scand Suppl. 2013;(196):38-47.)

Lyme activists, and even quack members of ILADS, long ago gave up trying to update or even defend the ILADS guidelines for Lyme disease treatment and diagnosis.  Instead, they have devoted all of their energy to attacking the IDSA Guidelines.  In other words, they have nothing to offer has an alternative, preferring instead to undermine the only current, evidence-based guidance available.

 

Anti-Science Politics Down East

Lyme disease bill pits frustrated patients against the medical mainstream

By Jackie Farwell, Bangor Daily News

Posted June 08, 2013

[snip]

Years of tests and treatments brought no relief, further deterioration of Sally’s health and more confusion.

It wasn’t until Dr. Charles Ray Jones, a Connecticut pediatrician and polarizing figure in the Lyme debate, diagnosed Sally with the disease in December 2011 that the Brewer girl began to have hope. Jones has treated thousands of patients for the disease with an unorthodox approach involving long-term antibiotics, and has collected powerful critics, loyal supporters and professional sanctions along the way.

Today, Sally remains on the antibiotics and is “feeling great,” she said. Well enough to travel to Augusta recently to testify in favor of a controversial bill that’s pitting Lyme disease patients against the medical mainstream.

The legislation, LD 597, would require the Maine Center for Disease Control and Prevention, the state’s official source of public health information, to include on its website information about “alternatives” for the treatment of Lyme disease.

The bill directs the Maine CDC to link to treatment guidelines for Lyme recommended by the International Lyme and Associated Diseases Society, a group that supports use of antibiotics over months and sometimes years to treat persistent or “chronic” cases of Lyme.

[snip]

“This is far and away the most irresponsible, misguided, and dangerous bill related to anything that I have any expertise with in all the years I’ve been in practice,” said Dr. Robert Pinsky, hospital epidemiologist at Eastern Maine Medical Center in Bangor, who has practiced in Maine for nearly 25 years.

The International Lyme and Associated Diseases Society’s “pseudoscience” view of Lyme has been repeatedly discredited and runs contrary to every major scientific organization, including not only the U.S. CDC, federal overseer of the Maine CDC, but also the National Institutes of Health and others, Pinsky said.

“This is essentially the same as if they were to pass a bill requiring Maine CDC to implicitly endorse the recommendations of groups that recommend against any childhood vaccination, or essentially endorsing views of groups that advocate that HIV is not the cause of AIDS,” he said.

The CDC and most doctors rely on the guidelines of the Infectious Disease Society of America, one of the nation’s largest medical organizations, in diagnosing and treating Lyme disease.

Pinsky said he regularly treats and provides consultations for patients erroneously diagnosed with Lyme and treated inappropriately by a small number of health providers who promote the International Lyme and Associated Diseases Society’s practices. Patients have been put at serious risk, both by delays in receiving accurate diagnoses and by ill-conceived antibiotic treatment that has been shown, in several large randomized clinical trials, to offer no greater benefit than placebo, Pinsky said. Some of his patients have suffered life-threatening complications from the treatment, he said.

[snip]

A proposed amendment to the hotly debated legislation would drop the requirement that the Maine CDC’s website link to the International Lyme and Associated Diseases Society, but instead to Lyme advocacy groups, which support the society’s views. Sponsored by Rep. Sheryl Briggs, D-Mexico, the bill is due for further debate in the House and Senate next week.

The bill’s supporters are targeting not only the Maine CDC, but also conversations about Lyme in the doctor’s office. The legislation would require health care providers who order a lab test for Lyme disease to inform patients that a negative test may not definitively mean that Lyme isn’t present, as well as discuss retesting and additional treatment.

[snip]

Sen. Geoff Gratwick, a Bangor Democrat and rheumatologist, said while Lyme disease is a serious problem that causes terrible suffering, politicians have no place inserting themselves in the doctor-patient relationship.

“I think that’s a very bad precedent for legislators to be saying how any group practices their craft,” he said.

The Maine Medical Association strongly opposes the bill’s “anti-science requirements.”

Testing for Lyme is just as accurate as for most other infectious disease, from strep throat to measles, but singling out Lyme for a special disclosure by doctors could give patients the opposite impression, Pinsky said.

“There’s nothing unique about Lyme disease in that regard,” he said. “The testing that’s available for Lyme disease is every bit as accurate as for virtually every other infectious disease that I see. It has limitations, but the limitations that are being promoted are not based in science.”

[snip]

Confederate Lyme?

Kerry L. Clark, Brian Leydet, and Shirley Hartman. Lyme Borreliosis in Human Patients in Florida and Georgia, USA. International Journal of Medical Sciences. 2013; 10(7):915-931. doi: 10.7150/ijms.6273.

The aim of this study was to determine the cause of illness in several human patients residing inFlorida and Georgia, USA, with suspected Lyme disease based upon EM-like skin lesions and/orsymptoms consistent with early localized or late disseminated Lyme borreliosis. Using polymerase chain reaction (PCR) assays developed specifically for Lyme group Borrelia spp., followed by DNA sequencing for confirmation, we identified Borrelia burgdorferi sensu lato DNA in samples of blood and skin and also in lone star ticks (Amblyomma americanum ) removed from several patients who either live in or were exposed to ticks in Florida or Georgia. This is the first report to present combined PCR and DNA sequence evidence of infection with Lyme Borrelia spp. in human patients in the southern U.S., and to demonstrate that several B. burgdorferi sensu lato species may be associated with Lyme disease-like signs and symptoms in southern states. Based on the findings of this study, we suggest that human Lyme borreliosis occurs in Florida and Georgia, and that some cases of Lyme-like illness referred to as southern tick associated rash illness (STARI) in the southern U.S. may be attributable to previously undetected B. burgdorferi sensu lato infections.

Unfortunately, the investigators seem to have failed in their aim to determine what exactly is infecting people in the southern states.  It may be due to relying on too few clinical samples collected from a variety of physicians and locations over the course of a decade, and then relying largely on PCR and DNA sequencing to diagnose a possible prior infection.  The authors note:

In this study we failed to isolate spirochetes from blood and skin biopsies from several patients from Florida and Georgia, despite identifying B. burgdorferi sensu lato DNA in their blood, skin, or previously attached ticks. This may have been due to using a low volume of patient fluid samples, a low number of spirochetes in the samples that could not be detected via culture, orperhaps the strains infecting patients in this region do not grow well in BSK-H medium. Culture isolation in BSK medium is known to be selective for specific genotypes of B. burgdorferi sensu lato.

Our findings represent the first report implicating B. americana in human infection, and raise the question of whether B. americana strains are responsible for other human cases of Lyme-like illness in the southern USA and elsewhere, since strains of this group have also been identified in California.

Our findings suggest that some cases of STARI resembling Lyme borreliosis in the southern U.S. may be attributable to previously undetected Lyme Borrelia strains, and thus represent cases of actual Lyme borreliosis rather than a separate disease entity or tick hypersensitivity reactions.

I think Jim Oliver and others have probably done a better job of identifying emerging borrelia pathogens as noted below in some relevant abstracts.  Importantly, they suggest “what was not considered Lyme borreliosis before might be now.”  Perhaps that true also of STARI.

 

Ticks Tick Borne Dis. 2011 Sep;2(3):123-8.  Updates on Borrelia burgdorferi sensu lato complex with respect to public health.Rudenko N, Golovchenko M, Grubhoffer L, Oliver JH Jr.

Borrelia burgdorferi sensu lato (s.l.) complex is a diverse group of worldwide distributed bacteria that includes 18 named spirochete species and a still not named group proposed as genomospecies 2. Descriptions of new species and variants continue to be recognized, so the current number of described species is probably not final. Most of known spirochete species are considered to have a limited distribution. Eleven species from the B. burgdorferi s.l. complex were identified in and strictly associated with Eurasia (B. afzelii, B. bavariensis, B. garinii, B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B. valaisiana, and B. yangtze), while another 5 (B. americana, B. andersonii, B. californiensis, B. carolinensis, and B. kurtenbachii) were previously believed to be restricted to the USA only. B. burgdorferi sensu stricto (s.s.), B. bissettii, and B. carolinensis share the distinction of being present in both the Old and the New World. Out of the 18 genospecies, 3 commonly and 4 occasionally infect humans, causing Lyme borreliosis (LB) - a multisystem disease that is often referred to as the 'great imitator' due to diversity of its clinical manifestations. Among the genospecies that commonly infect people, i.e. B. burgdorferi s.s., B. afzelii, and B. garinii, only B. burgdorferi s.s. causes LB both in the USA and in Europe, with a wide spectrum of clinical conditions ranging from minor cutaneous erythema migrans (EM) to severe arthritis or neurological manifestations. The epidemiological data from many European countries and the USA show a dramatic increase of the diagnosed cases of LB due to the development of new progressive diagnostic methods during the last decades (Hubálek, 2009). Recently, the definition of the disease has also changed. What was not considered Lyme borreliosis before might be now.

J Clin Microbiol. 2009 Dec;47(12):3875-80.Delineation of a new species of the Borrelia burgdorferi Sensu Lato Complex, Borrelia americana sp. nov.  Rudenko N, Golovchenko M, Lin T, Gao L, Grubhoffer L, Oliver JH Jr.

Analysis of borrelia isolates collected from ticks, birds, and rodents from the southeastern United States revealed the presence of well-established populations of Borrelia burgdorferi sensu stricto, Borrelia bissettii, Borrelia carolinensis, and Borrelia sp. nov. Multilocus sequence analysis of five genomic loci from seven samples representing Borrelia sp. nov. isolated from nymphal Ixodes minor collected in South Carolina showed their close relatedness to California strains known as genomospecies 1 and separation from any other known species of the B. burgdorferi sensu lato complex. One nucleotide difference in the size of the 5S-23S intergenic spacer region, one substitution in 16S rRNA gene signature nucleotides, and silent nucleotide substitutions in sequences of the gene encoding flagellin and the gene p66 clearly separate Borrelia sp. nov. isolates from South Carolina into two subgroups. The sequences of isolates of each subgroup share the same restriction fragment length polymorphism patterns of the 5S-23S intergenic spacer region and contain unique signature nucleotides in the 16S rRNA gene. We propose that seven Borrelia sp. nov. isolates from South Carolina and two California isolates designated as genomospecies 1 comprise a single species, which we name Borrelia americana sp. nov. The currently recognized geographic distribution of B. americana is South Carolina and California. All strains are associated with Ixodes pacificus or Ixodes minor and their rodent and bird hosts.

Clin Microbiol Infect. 2011 Apr;17(4):487-93. The expanding Lyme Borrelia complex--clinical significance of genomic species? Stanek G and Reiter M.

Ten years after the discovery of spirochaetes as agents of Lyme disease in 1982 in the USA, three genomic species had diverged from the phenotypically heterogeneous strains of Borrelia burgdorferi isolated in North America and Europe: Borrelia afzelii, B. burgdorferi sensu stricto (further B. burgdorferi), and Borrelia garinii. Whereas B. burgdorferi remained the only human pathogen in North America, all three species are aetiological agents of Lyme borreliosis in Europe. Another seven genospecies were described in the 1990s, including species from Asia (Borrelia japonica, Borrelia turdi, and B. tanukii), North America (Borrelia andersonii), Europe (Borrelia lusitaniae and Borrelia valaisiana), and from Europe and Asia (Borrelia bissettii). Another eight species were delineated in the years up to 2010: Borrelia sinica (Asia), Borrelia spielmanii (Europe), Borrelia yangtze (Asia), Borrelia californiensis, Borrelia americana, Borrelia carolinensis (North America), Borrelia bavariensis (Europe), and Borrelia kurtenbachii (North America). Of these 18 genomic species B. afzelii, B. burgdorferi and B. garinii are the confirmed agents of localized, disseminated and chronic manifestations of Lyme borreliosis, whereas B. spielmanii has been detected in early skin disease, and B. bissettii and B. valaisiana have been detected in specimens from single cases of Lyme borreliosis. The clinical role of B. lusitaniae remains to be substantiated.

Kerry Clark, the lead author of this Florida/Georgia study has done some good work with Jim Oliver and he should probably continue to work with him.  Right now he’s underfunded and his current role as an “expert consultant and member of the Northeast Florida Lyme Association, a local Lyme disease support and action group” probably doesn’t help. He’s the recipient of a grant from the N.J. Lyme Disease Association and has had other funding from the Northeast Florida Lyme Association, the Georgia Lyme Disease Association (GALDA), and “gifts by numerous private individuals to Dr. Clark’s UNF research foundation account.” Technical assistance in coordinating sample and data collection from several patients from Georgia was also provided by GALDA.  With those kinds of associations people may wonder whether he’s an activist or an investigator.  It’s difficult to be both.