​Following the release of the Draft Federal Framework on Lyme disease (Feb. 7, 2017), the CLSA issued a detailed critique highlighting numerous inadequacies of this document. Major shortcomings included inaccurately restrictive definitions of the Lyme disease-causing pathogens and their vectors, omission of meritorious scientific evidence, and disenfranchisement of patients and other key stakeholders.
 
The updated Framework (May 30, 2017) now includes modest improvements to surveillance strategies, such as:

• Identifying co-infections as a priority,
• Integrating data from veterinarians,
• Expanding human surveillance efforts to include those patients who do not adhere to strict case definitions.

 
Unfortunately, however, the Framework still largely fails to deliver on the legislated mandate of Bill C-442. Instead, it continues to endorse outdated treatment guidelines while disregarding the considerable body of scientific evidence amassed over the past decade. Many of the concerns we initially raised with the Draft are equally true of this revision. We are deeply disappointed that no further efforts have been made to capture and represent the modern biomedical perspective, or to integrate the experiences and needs of patients.
 
Ultimately, An Act respecting a Federal Framework on Lyme Disease was intended to facilitate constructive collaboration between political, clinical, academic, and patient sectors, in pursuit of solutions to the growing threat of Lyme disease. A major goal was to reduce the suffering associated with delayed diagnosis and prolonged complications. These objectives simply will not be possible without first bringing the full extent of evidence to bear, and inviting all stakeholders to the table.

In an interview on March 10, 2017, on CBC radio (Ottawa Morning), Dr. Caroline Quach, the president of Association of Medical Microbiology and Infectious Disease Canada made the following statements.

“I think that when we come up with a framework or with guidelines, what we really want is to have evidence-based data and so I think that patient experience will come in there. As you know there is a problem that needs to be addressed; now how it will be addressed is unclear to most of us right because if there’s we need to better educate the population on how to prevent Lyme disease; we also need to have money to do research, and to understand why these people are suffering, and what’s actually causing their illness. So, in terms of that framework, I think it’s a basis for a start of a conversation. Where it will end is impossible to know.”

We agree completely that this is a conversation that needs to happen. And we agree completely that the conversation and actions need to be evidence based. Regrettably, during the interview Dr. Quach made 8 statements relating to science, of which 6 were factually incorrect.

We trust that Dr. Quach did not really mean to imply that patients should be forced to participate in experimental trials when she said “aside from doing research, and from studying patients, making them enter trials, having clinics where these patients could be treated and tested, I don’t think that there’s a way to actually be able to know what’s happening.” But if the federal framework Lyme conference showed nothing else, it showed that we know very little about this disease and that there is a chasm between the research priorities of Lyme patients and AMMI. This makes it critical to include Lyme patients​ as equal partners in every stage of our response to this disease. This chasm needs to be breached and communication that is both respectful and accurate is required.

The comments from Dr. Quach, followed by a summary of the findings of that topic from the current peer-reviewed scientific literature are below.

1.  “In fact what happens is that currently there is no scientific evidence in the medical literature that Lyme Disease can become chronic”.
“… but once treated with anti-microbials for um a maximum of 4-6 weeks, sometimes with a repeater treatment, there’s no evidence that it actually becomes chronic …”
There are numerous investigations performed by unrelated research teams that utilized a variety of model systems, both in vitro and in vivo in organisms from mice to monkeys and humans, have demonstrated evidence of residual Borrelia following acute infection and antimicrobial intervention (1-4). Although the case is far from closed, the scientific and medical communities would be deeply remiss to ignore the evidence that continues to amass.

2.  Quach: “And so, that laboratory when you pay for your test to be sent there will diagnose you with Lyme, whereas it wouldn’t be picked up in and not diagnosed because it’s not Lyme.”
It is unclear which laboratory is under discussion here, however, most private Lyme disease testing includes serological diagnostics based on ELISA and Immunoblot (Western blot) testing. These methodologies are well established and routinely used in Borrelia testing, as well as for the testing of many other diseases. What is in dispute in the context of Lyme borreliosis is the algorithm used to evaluate the test results. Both the testing and the algorithms in private laboratories were well described by Fallon et al. (2014) (5). All the laboratories provided results with good sensitivities, the specificity was poor only if multiple inappropriate interpretations of the results were used. It should also be noted that no laboratories provide a diagnosis – this is provided by a physician -and that the payment is rendered for the test not the result; the payment is not altered by the test result and the implication that people purchase specific test outcomes is both incorrect and libelous.
 
3. “What we know is that Lyme disease is transmitted by a tick bite …”
This statement is correct, has been known for some decades(6) and is not contested. What is more problematic is the possibility of other modes of transmission.

Presenter: “On yesterday’s show we heard here that research into Lyme disease still of course very much a live topic, it’s ongoing: And we also heard that it may be possible to transmit the disease in ways not previously considered or talked about very much at least, namely that the disease may be transferred in the womb or through sexual contact or through mosquitoes. What is your feeling about that? Can Lyme Disease be transmitted in the womb, for example?”

Quach:  “Well then again, there’s no evidence that that is actually um happening. And in fact even in animal models, in mice that were infected with Lyme disease did not transmit it to their offspring. So there’s no animal models to support it and hasn’t been any evidence in the, in humans that that has happened, at least not reported in the literature. I think that as for everything we have peer review journals that review articles from scientists and so as long as that data is not available to the medical literature, to us at least there’s no proof that it actually happens, so [transmission is not] from breast milk or through sexual contact or through mosquito bites.

4. Congenital transmission:
There are certainly case reports of congenital infection of Borrelia and related tick vectored diseases in humans. (7-9) These tend to be older and the power of more recent epidemiological studies in humans was insufficient to resolve this issue.(10-12) Moreover, most human studies have focused on the potential of Borreliosis to cause adverse pregnancy outcomes, and did not focus on the long-term health of the child.(33) In animal models, Gustafson et al. 1993 (13) did find congenital transmission in dogs and Burgess et al (1993) in wild mice (14). While it is correct that Silver et al (1995) (15) showed that infected mice did not pass the infection to their pups it is also important to note that they did report significant mortality of the pups of infected mothers. These findings are of obvious concern to pregnant mothers and deserves to be better assessed.

5 Sexual transmission: There is considerable evidence in animal studies of contact transmission, of which sexual transmission is one type, in diverse animals including mice, dogs, horses, cows and ducks. (16-26) There are, of course, also published papers where such evidence was not found. (27-29) There is one paper, albeit contentious (as is so much with Lyme) reporting isolation of viable B. burgdorferi in human genital secretions. (30)

6. Mosquitoes as vectors: There are certainly reports of mosquitoes carrying Borrelia sp. (31, 32) This does not mean that mosquitoes are vectors. But given the abundance of mosquitoes, it does mean that the vectoral capacity of the mosquito species present in Canada should be directly addressed rather than dismissed.

7. Breast milk: Indeed, transmission of Borrelia has not been found in cow or human breast milk but this area remains relatively poorly investigated. (14, 33)

8. Currently it’s really being transmitted through Lyme tick bites – [ticks] that need to be attached to the human for at least 36 hours..”
Cook (2015) (34) provides an extensive review on this subject. Transmission time depends on the tick species, host species and prior tick activity (interrupted feeding). Cases of transmission within 24 hours have been documented in animal studies and in humans (35).
 
1. Rudenko N, Golovchenko M, Vancova M, Clark K, Grubhoffer L, Oliver JH Jr. 2016. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. Clin Microbiol Infect 22:267.e9–267.e15.

2. Hodzic E, Imai D, Feng S, Barthold SW. 2014. Resurgence of Persisting Non- Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice. PLoS ONE 9:e86907–12.

3. 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.

4.Hunfeld KP, Ružić-Sabljić E, Norris DE, Kraiczy P, Strle F. 2005. In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy. Antimicrob Agents Chemother 49:1294–1301. 
​
5. Fallon BA, Pavlicova M, Coffino SW, Brenner C. A comparison of lyme disease serologic test results from 4 laboratories in patients with persistent symptoms after antibiotic treatment. Clin Infect Dis. 2014 Dec 15;59(12):1705-10. doi: 10.1093/cid/ciu703.
 
6. (Burgdorfer W, Barbour AG, Hayes SF, Benach JL, Grunwaldt E, Davis JP (June 1982). "Lyme disease-a tick-borne spirochetosis?". Science. 216 (4552): 1317–9. Bibcode:1982Sci...216.1317B. doi:10.1126/science.7043737. PMID 7043737.).

7. Weber K, Bratzke H-J, Neubert U, Wilske B, Duray PH. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. The Pediatric Infectious Disease Journal. 1988;7(4):286–288. doi:10.1097/00006454-198804000-00010.
 
8. Schlesinger PA, Duray PH, Burke BA, Steere AC, Stillman MT. Maternal-fetal transmission of the Lyme disease Spirochete, Borrelia burgdorferi. Annals of Internal Medicine. 1985;103(1):67. doi:10.7326/0003-4819-103-1-67.
 
9. Brzostek T. [Human granulocytic ehrlichiosis co-incident with Lyme borreliosis in pregnant woman--a case study] [in Polish] Przegl Epidemiol. 2004;58(2):289–94.
 
10. Strobino BA, Williams CL, Abid S, Ghalson R, Spierling P. Lyme disease and pregnancy outcome: A prospective s of two thousand prenatal patients. American Journal of Obstetrics and Gynecology. 1993;169(2):367–374. doi:10.1016/0002-9378(93)90088-z.
 
11. Markowitz LE, Steere AC, Benach JL, Slade JD, Broome CV. Lyme disease during pregnancy. JAMA: The Journal of the American Medical Association. 1986;255(24):3394. doi:10.1001/jama.1986.03370240064038.
 
12. Maraspin V, Cimperman J, Lotric-Furlan S, Pleterski-Rigler D, Strle F. Erythema migrans in pregnancy. Wiener klinische Wochenschrift. 2000;111:933–40.
 
13. Gustafson JM, Burgess EC, Wachal MD, Steinberg H. Intrauterine transmission of Borrelia burgdorferi in dogs. American Journal of Veterinary Research. 1993;54(6):882–890.
 
14. Burgess EC1, Wachal MD, Cleven TD.Borrelia burgdorferi infection in dairy cows, rodents, and birds from four Wisconsin dairy farms. Vet Microbiol. 1993 May;35(1-2):61-77.
 
15. Silver RM, Yang L, Daynes RA, Branch WD, Salafia CM, Weis JJ. Fetal outcome in Murine Lyme disease. Infection and Immunity. 1995;63(1):66–72.
 
 
16.Bosler EM, Schulze TL. (1986) The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts. Zentralbl Bakteriol Mikrobiol Hyg A. 263(1-2):40-4.
 
17.Burgess EC, Amundson TE, Davis JP, et al.: Experimental inoculation of Peromyscus spp. with Borrelia burgdorferi: evidence of contact transmission. Am J Trop Med Hyg. 1986; 35(2): 355–9.
 
18.Burgess EC, Patrican LA: Oral infection of Peromyscus maniculatus with Borrelia burgdorferi and subsequent transmission by Ixodes dammini. Am J Trop Med Hyg. 1987; 36(2): 402–7.
 
19.Burgess EC: Experimental inoculation of mallard ducks (Anas platyrhynchos platyrhynchos) with Borrelia burgdorferi. J Wildl Dis. 1989; 25(1): 99–102.
 
20.Burgess EC: Experimentally induced infection of cats with Borrelia burgdorferi. Am J Vet Res. 1992; 53(9): 1507–11.
 
21.Burgess EC. (1986) Experimental inoculation of dogs with Borrelia burgdorferi. Zentralbl Bakteriol Mikrobiol Hyg A. 263(1-2):49-54.
 
22.Burgess EC. (1988) Borrelia burgdorferi infection in Wisconsin horses and cows. Ann N Y Acad Sci. 539:235-43.
 
23.Cerri D, Farina R, Andreani E, Nuvoloni R, Pedrini A, Cardini G. (1994) Experimental infection of dogs with Borrelia burgdorferi. Res Vet Sci. 57(2):256-8.
 
24.Renal lesions associated with Borrelia burgdorferi infection in a dog.
Grauer GF, Burgess EC, Cooley AJ, Hagee JH. J Am Vet Med Assoc. 1988 Jul 15;193(2):237-9.
 
25.Greene RT, Levine JF, Breitschwerdt EB, Walker RL, Berkhoff HA, Cullen J, 21Nicholson WL. (1988) Clinical and serologic evaluations of induced Borrelia burgdorferi infection in dogs. Am J Vet Res. 49(6):752-7.
 
26. Wright SD, Nielsen SW: Experimental infection of the white-footed mouse with Borrelia burgdorferi. Am J Vet Res. 1990; 51(12): 1980–7.
 
27. Appel MJ, Allan S, Jacobson RH, Lauderdale TL, Chang YF, Shin SJ, Thomford JW, Todhunter RJ, Summers BA. (1993) Experimental Lyme disease in dogs produces arthritis and persistent infection. J Infect Dis. 167(3):651-64.
 
28. Moody KD, Barthold SW: Relative infectivity of Borrelia burgdorferi in Lewis rats by various routes of inoculation. Amer J Trop Med Hyg. 1991; 44(2): 135–9.
 
29. Woodrum JE, Oliver JH Jr: Investigation of venereal, transplacental, and contact transmission of the Lyme disease spirochete, Borrelia burgdorferi, in Syrian hamsters. J Parasitol. 1999; 85(3): 426–30.
 
30. Middelveen MJ, Burke J, Sapi E et al. Culture and identification of Borrelia spirochetes in human vaginal and seminal secretions [version 1; referees: 1 not approved]. F1000Research 2014, 3:309
(doi: 10.12688/f1000research.5778.1)
 
31. Melaun C, Zotzmann S, Santaella VG, Werblow A, Zumkowski-Xylander H, Kraiczy P, Klimpel S. Occurrence of Borrelia burgdorferi s.l. in different genera of mosquitoes (Culicidae) in Central Europe. Ticks Tick Borne Dis. 2016 Mar;7(2):256-63. doi: 10.1016/j.ttbdis.2015.10.018. Epub 2015 Nov 12.

32. Kosik-Bogacka DI, Kuźna-Grygiel W, Jaborowska M.Ticks and mosquitoes as vectors of Borrelia burgdorferi s. l. in the forested areas of Szczecin. Folia Biol (Krakow). 2007;55(3-4):143-6.

33. Mylonas I. Borreliosis during pregnancy: a risk for the unborn child? Vector Borne Zoonotic Dis. 2011 Jul;11(7):891-8. doi: 10.1089/vbz.2010.0102.
 
34 Cook M (2015) Lyme borreliosis: a review of data on transmission time after tick attachment. Int J Gen Med 8:1–8. doi: 10.2147/IJGM.S73791

35. 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. doi: 10.1016/j.diagmicrobio.2011.10.003

Re: Lyme Disease in Canada: A Draft Federal Framework
 
 
The Canadian Lyme Science Alliance (CLSA) is pleased to provide feedback on the draft Federal Framework, released February 7, 2017. Our organization represents professionals in the Canadian academic and clinical sectors who support rigorous and unbiased scientific dialogue, investigation, and action regarding Lyme borreliosis. It is our mandate to help ensure that Lyme surveillance, diagnostic, and treatment guidelines reflect a balanced scientific consensus, that patient stakeholders are involved in the process of policy development, and that resources are made available to support ongoing basic, translational, and clinical research endeavors to better characterize Lyme disease.
 
It is from this perspective that we offer input into the creation and enactment of the Framework. All factors considered, we are disappointed by the lack of depth in this document, and the absence of concrete plans, deliverables, and timelines. While the conference informing this Framework (May, 2016) did succeed in convening diverse voices and highlighting emerging science, this was unfortunately not reflected in the resulting Draft. The vague imprecision of the Framework, coupled with its lack of tangible agenda, leadership, and management, do not portray or predict progress in this field.
 
As feedback has been specifically sought on the three pillars of the Framework -  surveillance, guidelines, and awareness - we address each below, and consider the overall capacity of this Framework to effect meaningful and strategic change.
 
1.0) The CLSA petition for robust science and transparent policy.
 
Following Royal Assent of Bill C-442 in December, 2014, the CLSA recognized the potential of this Act to propel discovery, improve the lives of Canadians, and transform healthcare in this country. It was also apparent that the success and feasibility of these goals, and the specific deliverables outlined in the Act, would be contingent on a thorough, inclusive, critical, and transparent evaluation of all available meritorious scientific evidence, as well as meaningful integration of input from diverse stakeholders.
 
In anticipation of the Framework development process, we issued a petition to our community that made the following (summarized) requests:
 
i) Engage Lyme disease patient and advocacy group representatives in the process of guideline development.
 
ii) Undertake a transparent review of all available literature on the status of Lyme disease.
 
iii) Allocate resources to enable independent Canadian Lyme disease research.
 
iv) Consider the scientific and political Lyme disease dialogue an ongoing process.
 
The full petition, and a list of its signatories, can be found in Appendix I.
 
The disciplines of Lyme disease treatment and research are fraught with controversy (see Appendix I), and it is our unwavering belief that these impasses can only be reconciled by dispensing with outdated, harmful dogma and approaching problems from a fresh scientific perspective that is informed by modern evidence and techniques, while considering the full body of amassed work.
 
We also believe that the medical and scientific sectors have important roles to play in ensuring that national policy is founded on high quality, ethical science that represents the best curated knowledge. In that spirit, we hereby present the CLSA petition to the Framework development committee, the Public Health Agency of Canada (PHAC), and the Minister of Health, The Honourable Jane Philpott. (Appendix I).
 
 
2.0) Pillars of the Federal Framework
 
2.1) National Medical Surveillance
 
Many conference participants recognized the benefit of tracking LD incidence rates and estimating the Canadian disease burden. While in principle this is an admirable goal, it is currently hindered by artificially restrictive designations of vector, pathogen, endemicity regions, and clinical case definitions outlined in the Draft. For example, the Introduction refers to the etiologic agent as Borrelia burgdorferi, and indeed the diagnostic testing in Canada has been based upon reactivity to B. burgdorferi sensu stricto B31 (1). In actual practice, Lyme disease proper is also caused by additional organisms, B. garinii, and B. afzelli, that are captured under the classical B. burgdorferi sensu lato (s.l) designation (2). While these pathogens are traditionally believed to affect Europe and Asia, B. garinii has been identified in Atlantic Canada as well (3). Moreover, additional Borrelia strains that fall outside of the traditional Lyme definition are known human pathogens that have likewise been associated with Lyme-like illness in North America and Europe (2, 4).  Considering that standard Canadian diagnostic strategies are not designed to detect (presumed) ‘international’ strains, serology-based surveillance will likely underreport prevalence on these grounds alone.
 
Further complicating matters, the diversity of Canadian vector-competent ticks is more extensive than is suggested in the Draft. Beyond I. scapularis and I. pacificus, mentioned in the Introduction, I. affinis, I. dentatus, I. spinipalpis, and I. muris are capable of transmitting Lyme disease, and all have been found in Canada (5, 6). Therefore, restricting ecological surveillance measures to include only I.scapularis and I. pacificus (blacklegged ticks) will fail to capture the extent of the potential LD vector threat.
 
According to conventional PHAC protocol, suspected human LD cases are evaluated based on their proximity to known regions of blacklegged tick endemicity. This approach is problematic not only on the basis of vector tick diversity, as just discussed, but also due to the growing body of evidence demonstrating distribution of infected ticks across Canada by migratory birds (7, 8). As noted by Morshed and colleagues, “despite the potential for dispersal of pathogen-carrying ticks by migratory birds, health professionals often disregard tick-borne diseases in their differential diagnosis when patients live in nonendemic areas” (7).
 
Considering that the microbiology, entomology, and ecological distribution patterns of LD are more diverse than accounted for in current approaches to Lyme disease management, it is not apparent how the present Framework intends to improve upon this flawed model to generate realistic estimates of threat and burden.
 
2.2) Guidelines
 
The Framework identifies LD prevention, diagnostics, and treatment as priorities, noting ‘limitations’ encountered with conventional testing. Disappointingly, however, the Draft does not offer concrete plans to enable research in these areas, nor does it endeavour to position Canada in a leadership role. Rather, it is complacent in its unquestioning reliance on guidelines developed internationally and imported into this country. The Draft alleges that these recommendations are “based on the best available evidence known worldwide” (pg. 12) but offers no review of this evidence, nor explanation for the omission of an entire body of peer-reviewed basic and biomedical literature that contradicts the prevailing wisdom. As the referenced Infectious Diseases Society of America (IDSA) Guidelines (9) are also over 10 years old, they are inherently outdated and not reflective of modern findings. The framework thus implicitly demands faith-based acceptance of antiquated recommendations, which is both regressive and contrary to the fundamental essence of science and progress.
 
While it is beyond the scope of the CLSA response to include a comprehensive evaluation of the literature, we are dismayed that such a document was not produced from the Framework development process. Transparency should be of highest priority when addressing delicate and controversial topics that profoundly impact the lives and wellbeing of Canadians. The importance of reliable diagnostic and treatment guidelines cannot be overemphasized, and it is critical for stakeholders from all sectors to be able to trust the scientific processes by which they are developed.
 
Moreover, there is concerning evidence of a lack of due diligence and an absence of scientific rigor and candor in the perspectives espoused by representatives of both the IDSA and The Association of Medical Microbiology and Infectious Disease (AMMI), upon whom Canada depends for its guideline creation. Unfortunately, members of these “medical and scientific professional organizations” (pg. 12) have resorted to public name calling and schoolyard bullying tactics targeting vulnerable populations, instead of maintaining a high standard of educated, rational, and scholarly discourse. One need look no further than a 2011 publication in The Lancet Infectious Diseases for evidence of such behaviour (10). In a media statement released by AMMI on 14th October, 2014 (“Chronic Lyme Disease” Advocacy: First, Do No Harm; Appendix II) the organization makes several claims that are scientifically unsubstantiated, and additionally frames their position by underrepresenting and trivializing literature that contradicts the status quo. They attempt to discredit the notion of bacterial persistence by identifying the flaws in a single study on the subject (4.1.1, Appendix I). This stance, aligned with the comment in the Draft that “there is no definitive evidence that continuing symptoms represent an ongoing infection” is, at best, an oversimplification of a complex topic. Indeed, numerous investigations performed by unrelated research teams that utilized a variety of model organisms, from mice to monkeys and humans, have demonstrated evidence of residual Borrelia following acute infection and antimicrobial intervention (4, 11-13). Although the case is far from closed, the scientific and medical communities would be deeply remiss to ignore the evidence that continues to amass.
 
It must also be reiterated that the Federal Framework on Lyme Disease Act mandated stakeholder participation with the expectation that input from various sectors would inform the development of the Draft. While the Conference Summary captures many voices, this diversity is almost entirely absent from the resulting Framework.
 
Overall, guidelines that are not transparently developed, and instead appear predicated on explicit, pre-existing, and entrenched bias, will not be tolerated by Canadians seeking answers in their healthcare, nor by scientists and clinicians within and beyond the CLSA who endeavour to address this perplexing malady.
 
 
2.3) Education and Awareness
 
While it is certainly true that tick bite avoidance is a good strategy to minimize risk of Borrelia infection, it cannot be relied upon to curtail the spread of vector-borne infection in a land dominated by wilderness. This emphasis also assumes that transmission to humans has been thoroughly and unequivocally characterized, and found to be limited to ticks, while in fact some reports in the literature have suggested other potential sources of infection, including transplacental and sexual routes (14, 15).
 
 Clearly, prevention and clinical prophylaxis require accurate information conveyed to both practitioners and members of the public. As we have discussed in preceding sections, the lack of consensus on issues ranging from pathogen and tick vector identities through to diagnostic test reliability greatly limits the cogency of the educational message.
 
 
 
3.0) Summary Critique of the Framework
 
Page 6 of the Draft Framework identifies three ‘key principals’ that allegedly underpin this document, namely engagement and collaboration, evidence-based, and adaptability. Unfortunately, the content of the Framework does not align with these ideals. The Draft instead suggests that “involvement and collaboration of Lyme disease patients” was reduced to mere tokenism, that review of ‘evidence’ was limited to that which supports the status quo, and that ‘adaptability’ awaits forthcoming research that was, in fact, not prioritized by the Framework. Again, the absence of concrete deliverables and metrics for those outcomes render this Draft a superficial and disappointing treatment of a serious topic. We suggest that this document requires serious reconsideration and retooling in order to achieve its mandated purpose.
 
 
Sincerely,
 
 
Melanie K. B. Wills
Ph.D.
Co-founder and Director,
Canadian Lyme Science Alliance
www.lymesciencealliance.org
 
 

 
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. Franke J, Hildebrandt A, Dorn W. 2013. Exploring gaps in our knowledge on Lyme borreliosis spirochaetes – Updates on complex heterogeneity, ecology, and pathogenicity. Ticks and Tick-borne Diseases 4:11–25.

3. Smith RP, Muzaffar SB, Lavers J, Lacombe EH, Cahill BK, Lubelczyk CB, Kinsler A, Mathers AJ, Rand PW. 2006. Borrelia garinii in seabird ticks (Ixodes uriae), Atlantic Coast, North America. Emerg Infect Dis 12:1909–1912.

4. Rudenko N, Golovchenko M, Vancova M, Clark K, Grubhoffer L, Oliver JH Jr. 2016. Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with undefined disorders and symptoms not typical for Lyme borreliosis. Clin Microbiol Infect 22:267.e9–267.e15.

5. Ondrejicka DA, Morey KC, Hanner RH, Adamowicz S. 2017. DNA barcodes identify medically important tick species in Canada. Genome 60:74–84.

6. Scott JD, Clark KL. 2016. First Record of Ixodes affinis Tick (Acari: Ixodidae) Infected with Borrelia burgdorferi Sensu Lato Collected from a Migratory Songbird in Canada. J Bacteriol Parasitol 7:1–10.

7. Morshed MG, Scott JD, Fernando K, Beati L, Mazerolle DF, Geddes G, Durden LA. 2005. Migratory songbirds disperse ticks across Canada, and first isolation of the Lyme disease spirochete, Borrelia burgdorferi, from the avian tick, Ixodes auritulus. J Parasitol 91:780–790.

8. Scott JD, Anderson JF, Durden LA. 2012. Widespread Dispersal of Borrelia burgdorferi–Infected Ticks Collected from Songbirds Across Canada. Journal of Parasitology 98:49–59.

9. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. 2006. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases.

10.  Auwaerter PG, Bakken JS, Dattwyler RJ, Dumler JS, Halperin JJ, McSweegan E, Nadelman RB, O'Connell S, Shapiro ED, Sood SK, Steere AC, Weinstein A, Wormser GP. 2011. Antiscience and ethical concerns associated with advocacy of Lyme disease. Lancet Infect Dis 11:713–719.
 
11.Hodzic E, Imai D, Feng S, Barthold SW. 2014. Resurgence of Persisting Non-Cultivable Borrelia burgdorferi following Antibiotic Treatment in Mice. PLoS ONE 9:e86907–12.

12. 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.

13.  Hunfeld KP, Ružić-Sabljić E, Norris DE, Kraiczy P, Strle F. 2005. In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy. Antimicrob Agents Chemother 49:1294–1301.
14. Mylonas I. 2011. Borreliosis during pregnancy: a risk for the unborn child? Vector Borne Zoonotic Dis 11:891–898.
15. Middelveen MJ, Burke J, Sapi E, Bandoski C, Filush KR, Wang Y, Franco A, Timmaraju A, Schlinger HA, Mayne PJ, Stricker RB. 2014. Culture and identification of Borrelia spirochetes in human vaginal and seminal secretions. F1000Res.

Drs. Vett Lloyd and Melanie Wills will be representing the Canadian Lyme Science Alliance at the Federal Framework on Lyme Disease Conference in Ottawa. The conference, mandated under Bill c-442, brings together patients, practitioners, policymakers, and researchers, to consider the present state of Lyme disease in Canada, and work toward a future in which this threat is mitigated. 

The conference will address the following topics, as reported by the Government of Canada website:

• medical surveillance for tracking:
  • incidence rates
  • associated economic costs
• standardized educational materials:
  • for use by Canadian public health providers
  • to increase national awareness
• guidelines and best practices regarding:
  • treatment
  • prevention
  • identification
  • management

(From: http://healthycanadians.gc.ca/diseases-conditions-maladies-affections/disease-maladie/lyme/federal-framework-conference-cadre-federal/index-eng.php)

The CLSA submitted the following brief to the The Standing Committee on Social Policy regarding their review of Bill 27, An Act to require a provincial framework and action plan concerning vector-borne and zoonotic diseases. 

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June 1, 2015
Summary:
The Canadian Lyme Science Alliance (CLSA), representing both academic researchers and clinical practitioners, is dedicated to enhancing our understanding of Lyme disease, and ensuring that health policy accurately reflects available scientific data. We suggest the following amendments to Bill 27, as explained in more detail below.

1. Inclusion of patients in the process of guideline development.
   
2. Consultation of independent experts.
   
3. Generation of a report summarizing the methods and literature used to establish Lyme disease surveillance, testing, and treatment protocols. 
   

Brief:
On behalf of the Canadian Lyme Science Alliance (CLSA), we are pleased to provide feedback regarding Bill 27, An Act to require a provincial framework and action plan concerning vector-borne and zoonotic diseases, on the occasion of its June 1st public hearing before The Standing Committee on Social Policy. We wish to comment on the Bill particularly as it applies to Lyme disease. 

Lyme borreliosis is a dangerous and debilitating bacterial disease transmitted through the bite of a tick vector. It occurs in multiple stages, with the first being characterized by localized infection at the site of tick attachment, that may be accompanied by an erythema migrans (EM) skin rash and flu-like symptoms. If untreated, the bacteria can spread throughout the body, giving rise to cardiac, musculoskeletal, and / or neurological manifestations (1). 
Overall, Lyme is a complex and incompletely characterized disease that is further confounded by controversy and highly polarized debate. The fate of both the bacteria and the patient in cases of longstanding infection (often termed Chronic Lyme Disease [CLD]), and the potential failure of antibiotic treatment to resolve symptoms (commonly referred to as Post Treatment Lyme Disease Syndrome, [PTLDS]) are hotly contested by medical professionals. Presently in Ontario, as in the rest of the country, there is no consensus on the definition, diagnosis, or management of these conditions. Yet, there is evidence that incidence of borreliosis is increasing in Canada, and is likely under-reported (2), making Lyme disease a high priority area of investigation.

The CLSA is a fledgling national organization that unites academics and clinicians in the quest for a more comprehensive understanding of Lyme disease. It 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. 

In principle, we strongly support efforts to improve surveillance, testing, and treatment of Lyme disease in Ontario, as well as initiatives that prioritize research in this field. However, we urge that the process of policy and guideline creation should be undertaken in the spirit of ethical scholarship and evidence-based medicine. We also strongly caution against adopting international guidelines without a thorough, transparent, and independent review of all available scientific literature. 

Earlier this year, the CLSA issued a statement to the Infectious Diseases Society of America (IDSA) as it endeavours to revise its Lyme disease guidelines. We argue that their proposed methodology does not constitute a best-practice approach to healthcare. Notably, the guideline authorship panel was deemed to lack diversity, as there is a strong clinical presence but marked deficit of basic researchers in relevant disciplines. Likewise, there is minimal representation from the community of scholars and practitioners who have published evidence supporting CLD or PTLDS - two of the most contentious and challenging aspects of this illness. Furthermore, the inclusion of a single ‘consumer representative’ with no disclosed knowledge of or experience with Lyme disease violates the Institute of Medicine (IOM) Standards for Developing Trustworthy Clinical Practice Guidelines, which call for “a current or former patient AND a patient advocate or patient/consumer organization representative” (3). 

Part of the mandate of the CLSA is to ensure that no published, peer-reviewed science is dismissed without scrutiny, and likewise, that existing protocols and international guidelines are not accepted or implemented unquestioningly. 

To this end, we have an active petition, currently generating support from the academic and clinical sectors, that requests several deliverables from the task force representing the Federal Framework on Lyme Disease (Bill C-442). Goals include involving patients and advocates in the process of policy development, undertaking a transparent review of available literature to generate solid, evidence-based guidelines, allocating resources to Canadian researchers to address deficits in the literature and identify uniquely Canadian perspectives on Lyme disease, and finally, ensuring that the Lyme disease dialogue remains open as new research becomes available. (Details available at www.lymesciencealliance.org)

We suggest that these objectives are broadly applicable to any contemporary initiatives to address Lyme disease. Thus, we recommend that Bill 27 be amended to specify:

1. The inclusion of patients and / or advocacy group representatives in the process of guideline creation, as outlined by The Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) (4).
   
2. The consultation of relevant, independent experts (researchers and clinicians) who can critically assess biomedical literature and determine the suitability of current and proposed techniques for evaluating and treating Lyme disease.
   
3. The generation of a publically available report summarizing the methods used by the guideline authors to arrive at their recommendations. This should include a critique of the scientific literature utilized, and provide justification in the event that any perspective supported by peer-reviewed science is dismissed and not addressed in the resulting surveillance, diagnostic, or therapeutic strategy. 
   

We would be pleased to endorse a Bill that incorporates these suggestions. We also invite your questions, comments, and requests for consultation, and 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. 


Sincerely,


Ms. Melanie K. B. Wills                                                                 Dr. Vett K. Lloyd
Co-founder, CLSA                                                                         Co-founder, CLSA
Ph.D. Candidate,                                                                           Ph.D., Professor
Molecular and Cellular Biology                                                  Department of Biology
University of Guelph                                                                    Mount Allison University


Select References

1. Borchers AT, Keen CL, Huntley AC, Gershwin ME. 2015. Lyme disease: A rigorous review of diagnostic criteria and treatment. J. Autoimmun. 57:82–115.

2. Sperling J, Middelveen M, Klein D, Sperling F. 2012. Evolving perspectives on lyme borreliosis in Canada. Open Neurol. J. 6:94–103.

3.     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].

4. Canadian Institutes of Health Research. Strategy for Patient-Oriented Research - Patient Engagement Framework. July 2 2014; Available at: http://www.cihr-irsc.gc.ca/e/48413.html [Accessed April 25, 2015].

In advance of today's tick and tick-vectored disease research conference in Moncton, NB, biology professor and CLSA co-founder Dr. Vett Lloyd spoke with CBC about the threat posed by ticks in the maritimes this year. 

"We're seeing more ticks than we have in any other year so I think it's going to be quite a busy year for ticks," Lloyd said.


"The frequency of infection with the Lyme disease bacteria is going up plus we're starting to see some new tick borne diseases showing up."

(Originally posted April 17, 2015)

The Canadian Lyme Science Alliance will be represented at the Maritime Tick and Tick Vectored Disease Research Conference in Moncton, NB, on May 9. The conference is open to the public, but the organizers ask that you register in advance.

For more information, see http://maritimetickconference.weebly.com

For those unable to attend, we will post highlights from the conference.

(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:

• 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].