Publish-Palooza!

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
velvetmagnetta
Posts: 469
Joined: Sun 23 Feb 2014 22:47

Publish-Palooza!

Post by velvetmagnetta » Wed 20 May 2015 9:24

Ooh...A furious publishing flurry ensues from the Infectious Diseases Clinics of North America -

The usual old news from the usual old suspects:

Hmm...Let's see..
From Halperin
Nervous System Lyme Disease
http://www.id.theclinics.com/article/S0 ... ct?rss=yes
(With the gall to use a Dickens quote! Because, you know, it's Halperin - friend to all the down-trodden)
How many long-proven falsehoods can you spot?
Lymphocytic meningitis, cranial neuritis or radiculoneuritis occur in up to 15% of patients with untreated Borrelia burgdorferi infection. Presentations of multifocal PNS involvement can range from painful monoradiculitis to confluent mononeuropathy multiplex. Serologic testing is highly accurate after 4 to 6 weeks of infection. In CNS infection, production of anti-B burgdorferi antibody is often demonstrable in CSF. Oral antimicrobials are microbiologically curative in virtually all patients, including acute European neuroborreliosis. Severe cases may require parenteral treatment. The fatigue and cognitive symptoms seen in some patients with extra-neurological disease are neither evidence of CNS infection nor specific to Lyme disease. (Source: Infectious Diseases Clinics of North America)
Just reading his "Key Points" is making my fatigue more severe. The usual playing down of post-treatment symptoms, denying that symptoms of memory loss and cognitive issues have anything whatsoever to do with a CNS infection, oh, and most people who think they have Lyme disease really don't have it...blah, blah, blah...

Next up: Lantos! Probably the best person to write about chronic Lyme disease.
Chronic Lyme Disease
http://www.id.theclinics.com/article/S0 ... ct?rss=yes

Chronic Lyme disease is a poorly defined diagnosis that is usually given to patients with prolonged, unexplained symptoms or with alternative medical diagnoses. Data do not support the proposition that chronic, treatment-refractory infection with Borrelia burgdorferi is responsible for the many conditions that get labeled as chronic Lyme disease. Prolonged symptoms after successful treatment of Lyme disease are uncommon, but in rare cases may be severe. Prolonged courses of antibiotics neither prevent nor ameliorate these symptoms and are associated with considerable harm.
Is it me or did Lantos just define pretty clearly the poorly defined concept of "chronic Lyme disease" by trying to argue its poorly defined nature?

At least PTLDS is recognized as "severe" finally - although nobody really has it. I think you all will really enjoy his "Key Points". I'm not sure how he knows this for I do not see any actual experiment done for this paper but he seems pretty adamant that "Persistent subjective symptoms during recovery from Lyme disease are not active infection."

OK. Mystery solved. We can all go home and suffer in silence with our unPost-Lyme symptoms from an inactive un-infection.


For this next piece, at least some unavoidable head-way was made:

Epidemiology of Lyme Disease
http://www.id.theclinics.com/article/S0 ... ct?rss=yes

Paul S. Mead

Lyme disease is the most common vector-borne illness in North America and Europe. The etiologic agent, Borrelia burgdorferi sensu lato, is transmitted to humans by certain species of Ixodes ticks, which are found widely in temperate regions of the Northern hemisphere. Clinical features are diverse, but death is rare. The risk of human infection is determined by the geographic distribution of vector tick species, ecologic factors that influence tick infection rates, and human behaviors that promote tick bite. Rates of infection are highest among children 5 to 15 years old and adults older than 50 years.
The above is not the abstract (it is just the paragraph that is under Lymenet Europe's News links - but you can read the abstract along with the "Key Points" if you click on the link.

About the Key Points: I know it doesn't look like much, especially while invoking the "endemic" concept as if it's not all over the freaking world by now, but Californians will be happy to see in these "Key Points" what Californians have already known for several decades: "...discrete areas of risk in Pacific Coast states."


Although I appreciate this next one, I still don't see any actual tests or experiments done to answer some of these questions that Aucott brings up - questions that have been brought up for years with no sign of an effort to answer them:
Posttreatment Lyme Disease Syndrome
http://www.id.theclinics.com/article/S0 ... ct?rss=yes
John M. Aucott, MD

The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this il...
He lists all the usual questions in his "Key Points" section like, what is PTLDS? Is it auto-immune? Is it damage" Is it continuing infection?

Well, Dr. Aucott, which is it? Can we dispense with the opinion papers and try an experiment or two? But hey, thanks for asking.


This next one confuses me a little...
Lyme Disease: Knowing Good Evidence to Help Inform Practice
Paul G. Auwaerter, MD
http://www.id.theclinics.com/article/S0 ... ct?rss=yes

Depending on the clinical situation and presence or absence of preconceived notions, evaluations for Lyme disease can range from efficient visits solved with a short course of antibiotic therapy to involved encounters that include a review of long-standing, nonspecific symptoms such as fatigue and pain that are less likely to represent an active infection. While the majority of patients with authentic Lyme disease improve with treatment, some have a slower resolution of symptoms and still others appear to have problems persisting beyond 6 months, which is called posttreatment Lyme disease syndrome (PTLDS).
Isn't Auwaerter the one who is searching for antibiotics and combinations of antibiotics to kill Lyme disease persisters? What, is he throwing in with both teams? Or did he have to publish this drivel to appease his buddies and keep his Boys Club membership?




It's always nice to see Lyme researchers working and publishing papers, but it's been a while since we have seen these players - but something's missing. What could it be? We have plenty of opinions and advice being doled out...but what about experiments? What about novel treatments methods?

What about some actual scientific work?

Lorima
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Joined: Mon 29 Oct 2007 20:47

Re: Publish-Palooza!

Post by Lorima » Wed 20 May 2015 14:32

I like your summary of the latest output.

Why no novel treatment trials?

I think it's largely because the dogma says that IDSA-style treatment is guaranteed to eradicate the bacteria. (Yes, there are holes in that, like Steere's longer treatment of some of this arthritis patients - but he's the Boss and can do what he wants. And the CDC survey findings that many patients are actually treated longer. But that is done under the table - the official dogma is still that there is no post-treatment infection.)

You aren't allowed by ethics committees to do human trials that aren't plausible, based on current understanding of the disease. So the dogma is actually preventing new treatment trials from occurring, aside from the fact that most researchers wouldn't risk their careers by defying the IDSA on LD. Aucott is doing the best that can be done, under the circumstances.

Mouse experiments are probably the best option under the circumstances, which is why Barthold and Baumgarth's work is so valuable. (Primates would be better but that work is so expensive that there is no way an "implausible" trial would be funded.) The trouble is that mice are not long-lived enough to study late-stage LD, and are enough different from humans in the details of drug response that I doubt a success in mice would be convincing to the ethics committees. Whereas a failure in mice, pretty much dooms the chance of any human studies. For example, here's a blog post on the tigecycline story:
http://spirochetesunwound.blogspot.com/ ... icate.html
(I haven't double-checked the details of this in the original sources, but I think it is likely to be accurate; the refs will steer you to the originals, if you want to check.)

I am puzzled by Auwaerter's presence on that persister paper. He is one of the most vehement editorial supporters of the IDSA model. Look at his PubMed record:
http://www.ncbi.nlm.nih.gov/pubmed/?term=auwaerter+p
So it seems really odd he would want his name on that publication. Maybe it is just a set-up to pretend that the persister data is being pursued? Or maybe he thinks he should hedge his bets; Aucott, at the same institution, is putting on some pressure. I suspect Auwaerter is just a careerist; I can't recall seeing anything original from him.

It is possible that this is what it looks like when an old, incorrect model finally starts breaking down publicly; certainly it doesn't happen all at once in a flood of recantation. But I'm not that optimistic; a new generation of CDC employees has been indoctrinated in the old dogma. If the field's academic leaders were considering changing their tune, wouldn't they tip off the CDC to start moderating their stance? On the other hand, I didn't think we Americans could elect someone whose name rhymes with Osama, so what do I know? ;)
"I have to understand the world, you see."
Richard Feynman

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ChronicLyme19
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Re: Publish-Palooza!

Post by ChronicLyme19 » Wed 20 May 2015 15:33

velvetmagnetta wrote:
Lymphocytic meningitis, cranial neuritis or radiculoneuritis occur in up to 15% of patients with untreated Borrelia burgdorferi infection. Presentations of multifocal PNS involvement can range from painful monoradiculitis to confluent mononeuropathy multiplex. Serologic testing is highly accurate after 4 to 6 weeks of infection. In CNS infection, production of anti-B burgdorferi antibody is often demonstrable in CSF. Oral antimicrobials are microbiologically curative in virtually all patients, including acute European neuroborreliosis. Severe cases may require parenteral treatment. The fatigue and cognitive symptoms seen in some patients with extra-neurological disease are neither evidence of CNS infection nor specific to Lyme disease. (Source: Infectious Diseases Clinics of North America)
Just on the number of CVID/immune deficient patients alone that is wrong. :bonk:
Lorima wrote: I am puzzled by Auwaerter's presence on that persister paper. He is one of the most vehement editorial supporters of the IDSA model. Look at his PubMed record:
Yeh, I am too. :?
Half of what you are taught is incorrect, but which half? What if there's another half missing?

TDP
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Joined: Fri 20 Mar 2015 16:55

Re: Publish-Palooza!

Post by TDP » Fri 22 May 2015 18:32

The usual IDSA crap:

Halperin: "Serologic testing is highly accurate after 4 to 6 weeks of infection." Rubbish - it has a negative predictive value of zero since there is at least one species, B. myamotoi, for which antigens are yet to be made commercially available. Assuming similar infectability as that of the burgdorferei complex, and given that recent studies (NL; UK) show that B. myamotoi infected ticks comprise about 15-20% of the infected population, even if there were no issues such as seronegativity and strain differences their over-hyped test would be at best 85% effective.

Mead: ignores the existence of species other than B.b.s.l.

Are these people really that ignorant of the literature?

RitaA
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Joined: Thu 1 Jul 2010 8:33

Re: Publish-Palooza!

Post by RitaA » Sat 23 May 2015 21:09

The Rel-Risk blogspot contains the following two entries. I've done my best to reproduce the bolding added by the blogger by using blue font here:

http://rel-risk.blogspot.com/2015/05/re ... ic-ld.html
Saturday, May 23, 2015

Review: Chronic LD

From a series of review papers published in Infectious disease clinics of North America.
Lantos PM. Chronic Lyme Disease. Infect Dis Clin North Am. 2015 Jun;29(2):325-340


Chronic Lyme disease (CLD) is a poorly defined term that describes the attribution of various atypical syndromes to protracted Borrelia burgdorferi infection. These syndromes are atypical for Lyme disease in their lack of the objective clinical abnormalities that are well-recognized in Lyme disease and, in many cases, the absence of serologic evidence of Lyme disease as well as the absence of plausible exposure to the infection. The syndromes usually diagnosed as CLD include chronic pain, fatigue, neurocognitive, and behavioral symptoms, as well as various alternative medical diagnoses—most commonly neurologic and rheumatologic diseases. Perhaps the most recognized and contentious facet of this debate is whether it is effective, appropriate, or even acceptable to treat patients with protracted antibiotic courses based on a clinical diagnosis of CLD.

The dialogue over CLD provokes strong feelings, and has been more acrimonious than any other aspect of Lyme disease. Many patients who have been diagnosed with CLD have experienced great personal suffering; this is true regardless of whether B burgdorferi infection is responsible for their experience. On top of this, many patients with a CLD diagnosis share the perception that the medical community has failed to effectively explain or treat their illnesses. In support of this patient base is a community of physicians and alternative treatment providers as well as a politically active advocacy community. This community promotes legislation that has attempted to shield CLD specialists from medical board discipline and medicolegal liability for unorthodox practices, to mandate insurance coverage of extended parenteral antibiotics, and most visibly to challenge legally a Lyme disease practice guideline. The advocacy community commonly argues that Lyme disease is grossly underdiagnosed and is responsible for an enormous breadth of illness; they also argue that the general scientific and public health establishments ignore or even cover up evidence to this effect. A large body of information about CLD has emerged on the Internet and other media, mostly in the forms of patient testimonials and promotional materials by CLD providers. For a medical consumer and for the physician unfamiliar with this subject, this volume of information can be confusing and difficult to navigate.

The CLD controversy does not, however, straddle a simple divide between 2 opposed scientific factions. Within the scientific community, the concept of CLD has for the most part been rejected. Clinical practice guidelines from numerous North American and European medical societies discourage the diagnosis of CLD and recommend against treating patients with prolonged or repeated antibiotic courses. Neither national nor state public health bodies depart from these recommendations. Within the medical community, only a small minority of physicians have accepted this diagnosis: 1 study found that only 6 of 285 (2.1%) randomly surveyed primary care physicians in Connecticut, among the most highly endemic regions for Lyme disease, diagnosed patients with CLD and still fewer were willing to prescribe long courses of antibiotics.

“Chronic Lyme disease,” however, has no clinical definition and is not characterized by any objective clinical findings. The only published attempt to define CLD provisionally produced a description too broad to distinguish CLD from myriad other medical conditions, and the case definition did not mention evidence of B burgdorferi infection (ILADS). The absence of a definition makes it impossible to investigate whether a patient population with putative CLD has evidence of infection with B burgdorferi; this would seem to be a basic requirement to include a syndrome within the term “Lyme disease.” It stands to reason that it is impossible to even posit a well-designed antibiotic trial when the study population is undefined.

Many patients referred for Lyme disease are ultimately found to have a rheumatologic or neurologic diagnosis. Rheumatologic diagnoses commonly misdiagnosed as Lyme disease include osteoarthritis, rheumatoid arthritis, degenerative diseases of the spine, and spondylo-arthropathies. Some patients are found to have neurologic diseases, including multiple sclerosis, demyelinating diseases, amyotrophic lateral sclerosis, neuropathies, and dementia. Some CLD advocates have argued that many patients referred for Lyme disease are ultimately found to have a rheumatologic or neurologic diagnosis. Rheumatologic diagnoses commonly misdiagnosed as Lyme disease include osteoarthritis, rheumatoid arthritis, degenerative diseases of the spine, and spondyloarthropathies. Some patients are found to have neurologic diseases, including multiple sclerosis, demyelinating diseases, amyotrophic lateral sclerosis, neuropathies, and dementia. Some CLD advocates have argued that these various conditions are simply manifestations of Lyme disease, but these hypotheses are untenable.

A limitation of modern medicine is our ability to explain and treat chronic pain, fatigue, and other disabling symptoms. It should come as no surprise that patients suffering from these symptoms have placed their hope in treatable conditions. Over time, a number of infectious diseases have been hypothesized as responsible, including Candida, Brucella, Epstein–Barr virus, xenotropic murine leukemia virus-related virus, and B burgdorferi. The scientific community has largely rejected chronic, treatment-refractory B burgdorferi infection, usually termed CLD, based on the absence of a defined patient population, the failure to detect cultivatable, clinically relevant organisms after standard treatment. Because the label CLD is applied to a highly heterogeneous spectrum of patients, the term CLD is better thought of as describing a phenomenon of attribution rather than a single disease. Even the subset of chronically symptomatic patients with a well-documented history of Lyme disease, usually termed PLDS, have little evidence of active infection, and their symptoms do not respond to antibiotics any better than to placebo. Controversies such as that over CLD are likely to persist for as long as patients suffer from poorly explained, disabling symptoms. We must hope that future research will provide better explanations and safe, effective treatments.
I think we can all agree with the last two sentences.

http://rel-risk.blogspot.com/2015/05/re ... st-ld.html
Saturday, May 23, 2015

Review: Post-LD

From a series of review papers published in Infectious disease clinics of North America.
Aucott JN. Posttreatment Lyme Disease Syndrome. Infect Dis Clin North Am. 2015, Jun;29 (2):309-323.


KEY POINTS

· Overall, prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause.

· Posttreatment Lyme disease syndrome (PTLDS) is characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy.

· PTLDS can vary markedly in disease severity from mild to severe symptoms with diminished health-related quality of life.

· Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease.

· Recommended treatment of PTLDS is largely symptom-based. There are currently no FDA-approved treatments for patients with PTLDS.


In general, the prognosis after treatment of uncomplicated infection with Borrelia burgdorferi, the causative agent of Lyme disease, is favorable. However, the clinical management of early or late-stage Lyme disease may in some cases be complicated by persistent fatigue, musculoskeletal, and cognitive symptoms after completion of standard antibiotic therapy. This documented constellation of patient-reported symptoms, which may be intermittent or constant, can be called posttreatment Lyme disease syndrome (PTLDS) when symptoms are prolonged for a period of 6 months or greater. Although objective findings, such as persistence of the erythema migrans rash (EM), cranial nerve palsy, meningitis, or radiculitis, may occasionally occur after treatment of early Lyme disease, these objective physical findings or laboratory manifestations more typical of untreated Lyme disease are not part of the clinical spectrum of PTLDS. Similarly, persistent joint synovitis may occur after repeated courses of antibiotic therapy for late Lyme arthritis and is also considered a distinct process, termed antibiotic-refractory late Lyme arthritis.

Despite extensive study of Lyme disease, PTLDS remains an enigmatic condition, because the underlying pathogenesis of the syndrome is not understood. The clinical validity of PTLDS as the sequelae of an infectious disease continues to be debated. One explanation is that the apparent association of symptoms after treatment of Lyme disease represents anchoring bias, incorrectly linking common nonspecific symptoms to an antecedent episode of Lyme disease. However, there is precedent for postinfectious syndromes of persistent fatigue following other infectious diseases, such as Epstein-Barr virus, Q fever, and Ross River virus. In one large study from Australia, 12% of those infected with these agents had persistent symptoms at 6 months. The investigators found that the presence of fatigue was predicted by the severity of initial symptoms, and was not predicted by psychological factors.

Overall, prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause. PTLDS is characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. PTLDS can vary markedly in disease severity from mild to severe symptoms with diminished health-related quality of life. The pathophysiology and mechanisms of persistent illness in PTLDS are not understood and there are little data on the effectiveness of nonantibiotic interventions. Risk factors for PTLDS include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Recommended treatment of PTLDS is largely symptom-based because there are currently no Food and Drug Administration–approved treatments for patients with PTLDS.

duncan
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Joined: Wed 5 Sep 2012 18:48

Re: Publish-Palooza!

Post by duncan » Sat 23 May 2015 21:46

I wonder if Lantos did all that writing himself. If so, he may wish to consider using a third party for edits, imho.

I would disagree with his suggestion that the most contentious point is over the efficacy of protracted treatments. I believe the most contentious debate is over whether Bb can persist after IDSA recommended therapy. It seems to me that the Lantos suggestion is a logical offshoot of the latter.

I take exception to his characterization of current proposed legislation. His seems a tad biased to me.

What's a CLD provider?

The concept of chronic Lyme disease has been rejected in Europe? I don't think so. Also, the only reason more people reject it in the US - presently - than accept it is because of who is broadly in control of the information spigot. That is slowly changing.

It's easy to define CLD. He should come to this Forum where we can supply him with an abundance of definitions. Moreover, CLD can be characterized by objective findings. People like him apparently just prefer to pretend that isn't so.

His Lyme-is-often-later-diagnosed-as-something-else paragraph largely could just be flip-flopped to read the exact opposite, i.e., that many of those afflictions can be imitated by Borrelia or other TBDs.

I love this particular sentence: "Even the subset of chronically symptomatic patients with a well-documented history of Lyme disease, usually termed PLDS, have little evidence of active infection..." First, it should be "...subset...has" , and I have to wonder how a Duke researcher - is he a Professor?? - cannot not know this elementary school level rule. Second, it really is no longer usually termed PLDS, at least not by the CDC; it's PTLDS. Third, that statement is just flat out inaccurate.

I've more, but I fear this will have to suffice for the time being. ;)

velvetmagnetta
Posts: 469
Joined: Sun 23 Feb 2014 22:47

Re: Publish-Palooza!

Post by velvetmagnetta » Sun 24 May 2015 19:55

Even the subset of chronically symptomatic patients with a well-documented history of Lyme disease, usually termed PLDS, have little evidence of active infection...
Even people with active infection have little evidence of active infection. What, exactly, are we using to measure active infection? I missed that part - the part that could end this entire debate!

RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Publish-Palooza!

Post by RitaA » Sun 24 May 2015 20:53

Here are two more entries from the Rel-Risk blogspot. I've done my best to reproduce the blogger's bolding by using blue font here:

http://rel-risk.blogspot.com/2015/05/re ... stics.html
Sunday, May 24, 2015

Review: Diagnostics

From a series of review papers published in Infectious disease clinics of North America.
Marques AR. Laboratory Diagnosis of Lyme Disease: Advances and Challenges. Infect Dis Clin North Am. 2015 Jun;29(2):295-307.


KEY POINTS

• It is difficult to demonstrate Borrelia burgdorferi by direct techniques (culture and polymerase chain reaction [PCR]). The spirochete is more easily found in the skin and plasma samples of patients with early disease (erythema migrans), and in the synovial fluid of patients with Lyme arthritis (using PCR).
• The sensitivity of antibody-based tests increases with the duration of the infection. Less than 50% of patients with erythema migrans are positive at presentation. These patients should receive treatment based on the clinical diagnosis.
• Serologic tests are most helpful in patients with clinical findings indicating later stages of Lyme disease.
• Many tests for Lyme disease are being performed in patients with low likelihood to have the disease, a situation in which a positive result is more likely to be a false-positive.
• The current assays do not distinguish between active and past infection, and patients may continue to be seropositive for years.
• The use of nonvalidated Lyme diagnostic tests is not recommended.

The available laboratory methods for the diagnosis of Lyme disease are in 2 categories: direct methods to detect B burgdorferi, and indirect methods that detect the immune response against it (mainly the detection of antibodies against B burgdorferi). It is important to recognize that laboratory tests should be ordered and interpreted in the context of the clinical evaluation and the likelihood that the patient has Lyme disease. This article reviews the laboratory diagnostics for Lyme disease (with focus on the United States) and discusses current recommendations and new developments.

The current 2-tier algorithm works well when used as recommended, but there are many areas for improvement. Problems include the low sensitivity during early infection, subjective interpretation of bands, and confusion by health care providers and patients regarding how to interpret results.

OTHER TESTS

The clinical usefulness of cell proliferation assays, Enzyme-Linked ImmunoSpot (ELISPOT) assays, cytokine measurements, complement split products, and lymphocyte transformation tests has not been established, and these tests should not be used for the diagnosis of Lyme disease. Natural killer cell measurements (CD57) are not helpful. Xenodiagnosis, using the natural tick vector (I scapularis) to detect evidence of infection in Lyme disease, is an experimental test, and its clinical applications depend on the results of future studies. Although xenodiagnosis is unlikely to be used in routine practice, it can offer researchers a tool to develop new tests for the disease.

http://rel-risk.blogspot.com/2015/05/re ... ology.html
Sunday, May 24, 2015

Review: LD Epidemiology

From a series of review papers published in Infectious disease clinics of North America.
Mead PS. Epidemiology of Lyme Disease. Infect Dis Clin North Am. 2015 Jun;29(2):187-210.


At least 18 distinct genospecies of Borrelia burgdorferi sensu lato have been described based on isolates obtained from small vertebrates or ticks. Most human infections are caused by 3 genospecies: B afzelii, B garinii, and B burgdorferi sensu stricto (hereafter referred to as B burgdorferi). Among these, only B burgdorferi causes Lyme disease in North America. Other genospecies occasionally isolated from humans include B spielmanii, B bavariensis, B valaisiana, B lusitaniae, and B bissetii. The public health importance of these other agents remains unclear. Additional genospecies will likely be identified as advanced molecular techniques are applied more broadly.

[graphic for Box 1: Named genospecies of Borrelia burgdorferi sensu lato]

Despite the high frequency of infection, few deaths caused by Lyme disease have been reported in the medical literature. A review of US death certificates identified 23 records during 1999 to 2003 that listed Lyme disease as the underlying cause of death; however, 11 were improperly coded, and only one listed a consistent causal sequence. The potential for occult death caused by Lyme carditis was demonstrated by a recent report of fatal Lyme carditis cases discovered through postmortem examination of donated tissues. Nevertheless, a follow-up study of more than 120,000 patients with Lyme disease during 1995 to 2013 found that only 0.6% died of all causes within a year of diagnosis, a rate less than the expected, age-adjusted, all-cause mortality for this population.

Although the epidemiology of Lyme disease is consistent with the well-established mechanism of transmission by Ixodes ticks, alternate modes of transmission have been investigated. Inoculation of blood with laboratory-adapted strains of B burgdorferi has demonstrated the organism’s ability to survive under blood banking conditions. Nevertheless, transmission by transfusion has never been documented. Meanwhile, transfusion-associated transmission of less common Ixodes-transmitted pathogens (Babesia, Anaplasma) has been demonstrated repeatedly.

There is also no credible evidence of transmission through sexual contact, semen, urine, or breast milk, despite a series of studies in animals. As described in the next section, the epidemiology of Lyme disease is the exact opposite of most sexually transmitted diseases, which are most common among persons aged 18 to 30 years. Intrauterine infection has been documented in rare reports of miscarriage and stillbirth in women infected during pregnancy. A causal relationship to miscarriage has not been established; however, as B burgdorferi has also been identified in placentas of women with normal pregnancy outcomes. Larger epidemiologic studies have identified no definable pattern of teratogenicity, and pregnant women who develop Lyme disease generally have good outcomes when they receive appropriate antimicrobial therapy.

Incidence of human Lyme disease typically ranges from 10 to 100 per 100,000 population in endemic states. The highest recorded statewide incidence was 134 per 100,000, reported in Connecticut in 2002 following implementation of mandatory laboratory-based reporting.

As shown for the years 2010 to 2013, Lyme disease incidence is bimodal with respect to age, with highest rates among children aged 5 to 15 years and adults older than 50 years. In the United States, the incidence is higher among males in all age groups.

Studies conducted in the 1990s yielded estimates of 3- to 12-fold underreporting for Lyme disease. These studies were limited to specific states and are not generalizable to national reporting. More recently, a survey of laboratory testing practices found that 7 large commercial laboratories tested approximately 2.4 million clinical specimens for Lyme disease in 2008, at a total estimated cost of $492,000,000. When applied to the estimated percentage of true infections within the source population (12%), this yielded an estimate of 288,000 (range 240,000–444,000) infected source patients in the United States in 2008. Approximately 35,000 Lyme disease cases were reported to the CDC during this same year, suggesting approximately 8-fold underreporting by this measure. Although this value likely represents a slight underestimate because it excludes patients for whom a laboratory testing was not conducted, it is comparable with estimates of underreporting for other nationally notifiable conditions.

Lyme disease poses special challenges for clinicians and public health alike. Diagnostic testing generally relies on serologic assays that are relatively insensitive for early forms of the disease. Furthermore, once a patient is seropositive, elevated antibody titers can persist for years. In a follow-up study of patients treated 10 to 20 years earlier, 28% to 63% of patients still had a positive immunoglobulin G response as determined by 2-tiered testing. The inability to distinguish acute from previous infection all but excludes laboratory-based reporting as an efficient mode of public health surveillance. Perhaps the most concerning challenge, however, is the ever-increasing number and distribution of cases. The ongoing emergence of Lyme disease underscores the urgent need for new and more effective interventions.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: Publish-Palooza!

Post by duncan » Sun 24 May 2015 21:13

Two quick observations about the Marques piece:

1) They seem to me somewhat self-serving, in particular the xenodiagnosis reference;

2) She seems to demonstrate quite effectively the lack of reliability, and hence utility, of the 2T criteria. Yet she does not seem aware of the ramifications to any verdicts of false negatives. More importantly, the no-win predicament such a position places patients who are treated, and endure treatment failure, continue to report symptoms and test positive via the 2T. By virtue of this diagnostic protocol, such patients may be doomed to a false diagnosis of Lyme-free. I find such a possible willingness unfortunate at best.

duncan
Posts: 1370
Joined: Wed 5 Sep 2012 18:48

Re: Publish-Palooza!

Post by duncan » Sun 24 May 2015 21:35

I hope everyone understands that this position means that late stage Lyme can be dismissed out of hand, if any kind of antibiotic treatment approximating IDSA guidelines has been rendered; technically, even if it hasn't, although that is less likely.

Someone - anyone - can contract Lyme, be symptomatic for Lyme, and even test positive for Lyme via the outrageous CDC 2Tier criteria, but still be refused a Lyme diagnosis.

Outrageous.

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