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.
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.