(April 10, 2015)
In 2015, Lyme disease treatment guidelines are up for review both in Canada and the United States. The Infectious Diseases Society of America (IDSA) issued an open call for public feedback on their Project Plan. The CLSA issued the statement below.
___
To Whom It May Concern:
On behalf of the Canadian Lyme Science Alliance (CLSA), I would like to thank you for this opportunity to provide feedback during the process of re-evaluating Lyme disease guidelines.
As you are undoubtedly aware, the strategy you are about to develop will have great impact not only on the lives of Americans, but also on the global community of Infectious Disease Societies and practitioners who look to the IDSA for sound, science-based medical guidance. The participation of the ESCMID and the Canadian AMMI in this process underscores the international significance of this undertaking, and thus, the responsibility held by this committee for the health and welfare of all our citizens.
The CLSA was founded by Canadian research scientists out of concern for the schism in medical literature and guidelines that currently divides scientists, clinicians, policymakers, and patients. We represent the voice of independent researchers and practitioners who call for an open, unbiased, and rigorous scientific dialogue surrounding Lyme borreliosis.
Presently in Canada, we are launching an academic petition in light of the ratification of the Private Member’s Bill C-442, to request a fair scientific inquiry into the biological complexities of Lyme borreliosis.
Points of debate include, but are not limited to, the following evidence:
Accordingly, we have identified the following requirements in order to begin resolving these critical discrepancies in the current understanding of Lyme borreliosis:
i) Engage Lyme disease patient and advocacy group representatives in the process of guideline development. Both the Institute of Medicine (IOM) and the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) emphasize the importance and value of meaningful patient involvement in medical governance.
We note that the inclusion of a single ‘consumer representative’, Ms. Jane Glazer Rips (page 2, line 31), does not satisfy this requirement. The IOM Standards for Developing Trustworthy Clinical Practice Guidelines specifically recommends that the Guideline Development Group include “a current or former patient AND a patient advocate or patient/consumer organization representative” (13). Furthermore, as Ms. Rips’ association with Lyme disease is not disclosed in the “Project Plan”, her suitability for this panel remains questionable.
ii) Undertake a transparent review of all available literature on the status of Lyme disease. This should be provided by an independent, interdisciplinary group of scholars representing fields including ecology, entomology, epidemiology, microbiology, immunology, biochemistry, molecular genetics, bioethics, health economics, and clinical practice. It must also be executed in accordance with IOM Standards for Developing Trustworthy Clinical Practice Guidelines, such that conflict of interest situations are revealed and resolved (13).
Of the 30 guideline authors listed on page 2, lines 3-40, only two appear to possess Ph.D. qualifications, while 29 are identified as MDs. This suggests that the panel lacks diversity and representation from the basic research community, and is instead overwhelmingly biased toward the clinical perspective. Considering the complexity of borreliosis, and the wide range of scientific disciplines that generate valuable translational data, we strongly urge you to adopt a balanced and collaborative approach that has the potential to integrate knowledge and transcend the current state of conflict and stagnation.
iii) Allocate resources to enable independent Lyme disease research. The current level of controversy surrounding LD demonstrates that the scientific understanding of Borrelia infection is far from complete. The report generated from point (ii) above will outline areas of specific concern, which should be deemed top priority foci of investigation.
iv) Consider the scientific and political Lyme disease dialogue an ongoing process.
As new, peer-reviewed scientific data become available, the guidelines and recommendations developed from points (i) – (iii) will require reassessment and refinement to reflect our evolving perspectives on Lyme borreliosis.
It is our hope that as the AMMI and IDSA embark on collaborative and independent guideline review processes this year, these standards of practice are upheld. Should we be given the opportunity, we would be delighted to apprise you of the support generated from Canada’s scientific and clinical communities for a fair and rigorous scientific inquiry into the complexities of Lyme disease.
We look forward to continued dialogue.
Select References
1. Sperling J, Middelveen M, Klein D, Sperling F. 2012. Evolving perspectives on lyme borreliosis in Canada. Open Neurol. J. 6:94–103.
2. Hynote ED, Mervine PC, Stricker RB. 2012. Clinical evidence for rapid transmission of Lyme disease following a tickbite. Diagn. Microbiol. Infect. Dis. 72:188–192.
3. Saraiva DG, Soares HS, Soares JF, Labruna MB. 2014. Feeding Period Required by Amblyomma aureolatumTicks for Transmission of Rickettsia rickettsiito Vertebrate Hosts. Emerg. Infect. Dis. 20:1504–1510.
4. Ogden NH, Margos G, Aanensen DM, Drebot MA, Feil EJ, Hanincova K, Schwartz I, Tyler S, Lindsay LR. 2011. Investigation of Genotypes of Borrelia burgdorferi in Ixodes scapularis Ticks Collected during Surveillance in Canada. Appl. Environ. Microbiol. 77:3244–3254.
5. Nowakowski J, Schwartz I, Liveris D, Wang G, Aguero-Rosenfeld ME, Girao G, McKenna D, Nadelman RB, Cavaliere LF, Wormser GP, Lyme Disease Study Group. 2001. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin. Infect. Dis. 33:2023–2027.
6. Stricker RB, Johnson L. 2011. Lyme disease: the next decade. Infect. Drug Resist. 4:1–9.
7. Aucott JN, Rebman AW, Crowder LA, Kortte KB. 2012. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual. Life Res. 22:75–84.
8. Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, Jacobs MB, Hasenkampf NR, Martin DS, Narasimhan S, Phillippi-Falkenstein KM, Purcell JE, Ratterree MS, Philipp MT. 2012. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE 7:e29914.
9. Feng J, Auwaerter PG, Zhang Y. 2015. Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline. PLoS ONE 10:1–15.
10. Stricker RB. 2007. Counterpoint: Long-Term Antibiotic Therapy Improves Persistent Symptoms Associated with Lyme Disease. Clin. Infect. Dis. 45:149–157.
11. DeLong AK, Blossom B, Maloney EL, Phillips SE. 2012. Antibiotic retreatment of Lyme disease in patients with persistent symptoms: A biostatistical review of randomized, placebo-controlled, clinical trials. Contemp. Clin. Trials 33:1132–1142.
12. Fallon BA, Petkova E, Keilp JG, Britton CB. 2012. A reappraisal of the u.s. Clinical trials of post-treatment lyme disease syndrome. Open Neurol. J. 6:79–87.
13. Institute of Medicine. Standards for Developing Trustworthy Clinical Practice Guidelines. Mar 23, 2011; Available at: http://www.iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust/Standards.aspx [Accessed April 7, 2015].
In 2015, Lyme disease treatment guidelines are up for review both in Canada and the United States. The Infectious Diseases Society of America (IDSA) issued an open call for public feedback on their Project Plan. The CLSA issued the statement below.
___
To Whom It May Concern:
On behalf of the Canadian Lyme Science Alliance (CLSA), I would like to thank you for this opportunity to provide feedback during the process of re-evaluating Lyme disease guidelines.
As you are undoubtedly aware, the strategy you are about to develop will have great impact not only on the lives of Americans, but also on the global community of Infectious Disease Societies and practitioners who look to the IDSA for sound, science-based medical guidance. The participation of the ESCMID and the Canadian AMMI in this process underscores the international significance of this undertaking, and thus, the responsibility held by this committee for the health and welfare of all our citizens.
The CLSA was founded by Canadian research scientists out of concern for the schism in medical literature and guidelines that currently divides scientists, clinicians, policymakers, and patients. We represent the voice of independent researchers and practitioners who call for an open, unbiased, and rigorous scientific dialogue surrounding Lyme borreliosis.
Presently in Canada, we are launching an academic petition in light of the ratification of the Private Member’s Bill C-442, to request a fair scientific inquiry into the biological complexities of Lyme borreliosis.
Points of debate include, but are not limited to, the following evidence:
- Lyme disease is likely underreported in Canada (1).
- Zoonotic transmission of Borrelia and other pathogens can occur rapidly and varies by pathogen, tick species and metabolic state (2, 3).
- The diversity of Borrelia species and strains in Canadian ticks is more extensive than predicted (4).
- Current two-tier diagnostic testing is not reliable. The sensitivity of this method has been estimated at ~40% for early acute Lyme disease, and 66% for convalescent cases (5). Measures of test accuracy in reporting late Lyme disease are particularly controversial (6).
- Persistent symptoms following infection and treatment cessation are not rare, giving rise to the phenomenon of Chronic Lyme Disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS). In a recent study, 36% of patients with acute Lyme went on to suffer symptoms subsequent to standard antibiotic intervention (7).
- B. burgdorferi can persist following the traditional treatment protocol (8), and this residual bacterial colonization has been postulated as a cause of CLD / PTLDS (6).
- Antibiotics can be of benefit in resolving underlying infection (9) and symptoms of CLD / PTLDS (10-12).
Accordingly, we have identified the following requirements in order to begin resolving these critical discrepancies in the current understanding of Lyme borreliosis:
i) Engage Lyme disease patient and advocacy group representatives in the process of guideline development. Both the Institute of Medicine (IOM) and the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) emphasize the importance and value of meaningful patient involvement in medical governance.
We note that the inclusion of a single ‘consumer representative’, Ms. Jane Glazer Rips (page 2, line 31), does not satisfy this requirement. The IOM Standards for Developing Trustworthy Clinical Practice Guidelines specifically recommends that the Guideline Development Group include “a current or former patient AND a patient advocate or patient/consumer organization representative” (13). Furthermore, as Ms. Rips’ association with Lyme disease is not disclosed in the “Project Plan”, her suitability for this panel remains questionable.
ii) Undertake a transparent review of all available literature on the status of Lyme disease. This should be provided by an independent, interdisciplinary group of scholars representing fields including ecology, entomology, epidemiology, microbiology, immunology, biochemistry, molecular genetics, bioethics, health economics, and clinical practice. It must also be executed in accordance with IOM Standards for Developing Trustworthy Clinical Practice Guidelines, such that conflict of interest situations are revealed and resolved (13).
Of the 30 guideline authors listed on page 2, lines 3-40, only two appear to possess Ph.D. qualifications, while 29 are identified as MDs. This suggests that the panel lacks diversity and representation from the basic research community, and is instead overwhelmingly biased toward the clinical perspective. Considering the complexity of borreliosis, and the wide range of scientific disciplines that generate valuable translational data, we strongly urge you to adopt a balanced and collaborative approach that has the potential to integrate knowledge and transcend the current state of conflict and stagnation.
iii) Allocate resources to enable independent Lyme disease research. The current level of controversy surrounding LD demonstrates that the scientific understanding of Borrelia infection is far from complete. The report generated from point (ii) above will outline areas of specific concern, which should be deemed top priority foci of investigation.
iv) Consider the scientific and political Lyme disease dialogue an ongoing process.
As new, peer-reviewed scientific data become available, the guidelines and recommendations developed from points (i) – (iii) will require reassessment and refinement to reflect our evolving perspectives on Lyme borreliosis.
It is our hope that as the AMMI and IDSA embark on collaborative and independent guideline review processes this year, these standards of practice are upheld. Should we be given the opportunity, we would be delighted to apprise you of the support generated from Canada’s scientific and clinical communities for a fair and rigorous scientific inquiry into the complexities of Lyme disease.
We look forward to continued dialogue.
Select References
1. Sperling J, Middelveen M, Klein D, Sperling F. 2012. Evolving perspectives on lyme borreliosis in Canada. Open Neurol. J. 6:94–103.
2. Hynote ED, Mervine PC, Stricker RB. 2012. Clinical evidence for rapid transmission of Lyme disease following a tickbite. Diagn. Microbiol. Infect. Dis. 72:188–192.
3. Saraiva DG, Soares HS, Soares JF, Labruna MB. 2014. Feeding Period Required by Amblyomma aureolatumTicks for Transmission of Rickettsia rickettsiito Vertebrate Hosts. Emerg. Infect. Dis. 20:1504–1510.
4. Ogden NH, Margos G, Aanensen DM, Drebot MA, Feil EJ, Hanincova K, Schwartz I, Tyler S, Lindsay LR. 2011. Investigation of Genotypes of Borrelia burgdorferi in Ixodes scapularis Ticks Collected during Surveillance in Canada. Appl. Environ. Microbiol. 77:3244–3254.
5. Nowakowski J, Schwartz I, Liveris D, Wang G, Aguero-Rosenfeld ME, Girao G, McKenna D, Nadelman RB, Cavaliere LF, Wormser GP, Lyme Disease Study Group. 2001. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin. Infect. Dis. 33:2023–2027.
6. Stricker RB, Johnson L. 2011. Lyme disease: the next decade. Infect. Drug Resist. 4:1–9.
7. Aucott JN, Rebman AW, Crowder LA, Kortte KB. 2012. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual. Life Res. 22:75–84.
8. Embers ME, Barthold SW, Borda JT, Bowers L, Doyle L, Hodzic E, Jacobs MB, Hasenkampf NR, Martin DS, Narasimhan S, Phillippi-Falkenstein KM, Purcell JE, Ratterree MS, Philipp MT. 2012. Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection. PLoS ONE 7:e29914.
9. Feng J, Auwaerter PG, Zhang Y. 2015. Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline. PLoS ONE 10:1–15.
10. Stricker RB. 2007. Counterpoint: Long-Term Antibiotic Therapy Improves Persistent Symptoms Associated with Lyme Disease. Clin. Infect. Dis. 45:149–157.
11. DeLong AK, Blossom B, Maloney EL, Phillips SE. 2012. Antibiotic retreatment of Lyme disease in patients with persistent symptoms: A biostatistical review of randomized, placebo-controlled, clinical trials. Contemp. Clin. Trials 33:1132–1142.
12. Fallon BA, Petkova E, Keilp JG, Britton CB. 2012. A reappraisal of the u.s. Clinical trials of post-treatment lyme disease syndrome. Open Neurol. J. 6:79–87.
13. Institute of Medicine. Standards for Developing Trustworthy Clinical Practice Guidelines. Mar 23, 2011; Available at: http://www.iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust/Standards.aspx [Accessed April 7, 2015].