I am writing this letter to you to express my serious concerns that your updated 2019 guidelines regarding the ‘Prevention, Diagnosis and Treatment of Lyme Disease’ are disturbingly and strangely silent to the very real documented risk of in-utero transmission of Borrelia burgdorferi. Members of your committee including Drs Steere , Wormser , Strle , Halperin,9 Aguero-Rosenfeld , and Belani have already acknowledged this alternate mode of transmission in the authorship or co-authorship of historical publications in top-tier peer-reviewed journals including primary research findings and/or commentaries or reviews of Lyme disease. Two former guidelines authors from the 2006 IDSA Clinical Practice guidelines who are not listed in the authorship of the updated guidelines, specifically Drs Dattwyler and Shapiro have also acknowledged and reported on mother to baby transmission of Borrelia burgdorferi.

Transplacental transmission, adverse outcomes and reports of congenital infection of Borrelia burgdorferi (Bb) have been clearly documented over the last 34 years (1985 to 2019) by multiple international physicians, pioneering researchers and scientists including Dr. Willy Burgdorfer (after whom Borrelia burgdorferi was named), Dr. Alan Steere (one of the primary investigators of Lyme disease in Lyme Connecticut and on your committee), Dr. Alan MacDonald
(pathologist who meticulously documented Borrelia burgdorferi in tissues of fetal autopsies) and Dr. Tessa Gardner (Pediatric Infectious Disease Specialist).

The Infectious Disease Society of America, American Academy of Neurology, and American Academy of Rheumatology jointly proposed Lyme disease guidelines. Four areas most relevant to psychiatry were reviewed—the disclaimer, laboratory testing, and adult and pediatric psychiatric sections. The disclaimer and the manner in which these guidelines are implemented are insufficient to remove the authors and sponsoring organizations from liability for harm caused by these guidelines. The guidelin…

Author: Robert Bransfield, MD

Proposed Lyme Disease Guidelines and Psychiatric Illnesses

Most Lyme groups agree that “the duration of tick attachment is among the most important predictors of subsequent Lyme Disease (LD)” but the situation is more complex than portrayed in the draft guidelines. To date, there is no study that has established the minimum tick attachment time for transmission of LD in humans. The draft guidelines imply that if the attachment is less than 36 hours the risk of bacterial transmission is low. Dr. Willy Burgdorfer the microbiologist who identified the bacteria that causes  Lyme disease acknowledged in a 2001 interview that “there are about 5 to 10 percent of infected ticks that have a generalized infection,” including it being present in their salivary glands and saliva at the time of attachment. “In such cases, transmission of spirochetes would and does occur immediately at time of attachment.” Unfortunately, many physicians are unaware that instantaneous transmission is possible.   A bite by an infected tick can have a 1/20-1/10 chance of rapidly passing on the illness, so that by the 36-hour mark, the bacteria can be spreading to multiple body sites.   There should be some mention that this rapid transmission can occur in the guidelines.

Rosalie Greenberg, MD

Psychiatrist

baredeso <baredeso@aol.com>

Persistence of The Lyme Disease Bacterium,Borrelia burgdorferi

The following references for persistence of Lyme disease (Lyme borreliosis) are listed alphabetically and chronologically:

1. Aalto A, Sjowall J, Davidsson L, Forsberg P, Smedby O. Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis. Acta Radiol 2007; 48: 755-762. [white matter hyperintensities or basal ganglia lesions].
2. AbeleDC and Anders KH. The many faces and phases of borreliosis. J Am AcadDermotol 1990; 23:401-410. [chronic Lyme borreliosis].
3. Aberer E and Klade H. Cutaneous manifestations of Lyme borreliosis. Infection 1991; 19: 284-286. [chronic Lyme borreliosis].
4. Aberer E, Breier F, Stanek G, and Schmidt B. Success and failure in the treatment of acrodermatitis chronica atrophicans skin rash. Infection 1996; 24: 85-87.
5. Aberer E, Kersten A, Klade H, Poitschek C, Jurecka W. Heterogeneity of Borrelia burgdorferi in the skin. Am J Dermatopathol 1996; 18(6): 571-519.
6. Ackermann R, Rehse-Küpper B, Gollmer E, Schmidt R. Chronic neurologic manifestations of erythema migrans borreliosis. Ann NY Acad Sci 1988; 539: 16-23.
7. Akin E, McHugh Gl, Flavell RA, Fikrig E, Steere AC. The immunoglobulin (IgG) antibody response to OspA and OspB correlates with severe and prolonged Lyme arthritis and the IgG response to P35 with mild and brief arthritis. Infect Immun 1999; 67: 173-181.
8. Albert S, Schulze J, Riegel H, Brade V. Lyme arthritis in a 12-year-old patient after a latency period of 5 years. Infection 1999; 27(4-5): 286-288.
9. Al-Robaiy S, Dihazi H, Kacza J, et al. Metamorphosis of Borrelia burgdorferi organisms―RNA, lipid and protein composition in context with the spirochete’s shape. J Basic Microbiol 2010, 50 Suppl 1, S5-17.
10. Appel MJG, Allan S, Jacobson RH, Lauderdale TL, Chang YF, Shin SJ, Thomford JW, Todhunter RJ, and Summers BA. Experimental Lyme disease +in dogs produces arthritis and persistent infection. J Inf Dis 1993; 167: 651-664.
11. Åsbrink E, Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans, Afzelius and acrodermatischronica atrophicans. Acta Pathol Microbiol Immunol Sect B 1985; 93: 161-163.
12. Åsbrink E, Hovmark A, and Olsson Clinical manifestations of acrodermatitis chronica atrophicans in 50 Swedish patients. ZentralblBakteriolMikrobiolHyg A 1986; 26: 253-261. [chronic Lyme borreliosis].
13. Asch ES, Bujak DI, Weiss M, Peterson MGE, and Weinstein A. Lyme Disease: an infectious and postinfectious syndrome. J Rheumatol 1994; 21 (3): 451-461.
14. Aslam B, Nisar MA, Khurshid M, Farooq-Salamat MK. Immune escape strategies of Borrelia burgdorferi. Future Microbiology 2017; 12: 1219-1237. https://doi.org/10.2217/fmb-2017-0013.
15. Bankhead T and Chaconas G. The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Molecular Microbiology 2007; 65: 1547-1558.
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17. Barthold SW, deSouza MS, Janotka JL, Smith AL, and Persing DH. Chronic Lyme borreliosis in laboratory mouse. Am J Pathol 1993; 143: 951-971. [in mice]
18. Barthold S. Lyme borreliosis. Chapter 14, In Persistent Bacterial Infections. Edited by J.P. Nataro, M.J. Blaser, and S. Cunningham-Rundles, pp 281-304. ASM Press, Washington, D.C.
19. Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, and Luft BJ. Ineffectiveness of tigecycline against persistent Borrelia burgdorferi. Antimicrob Agents Chemother 2010; 54(2): 643-651. [mice, rats, white-footed mice, hamsters, gerbils, guinea pigs, rabbits, dogs, nonhuman primates, and humans]
20. Barthold SW. Global challenges in diagnosing and managing Lyme disease—closing knowledge gaps. Testimony before House Committee on Foreign Affairs, United States Congress, 17 July 2012.
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23. Bayer ME, Zhang L, Bayer MH. Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Infection 1996; 24: 347-353. [97 patients who had been treated with antibiotics for extended periods of time and had symptoms of chronic Lyme were PCR-positive.]
24. de Leeuw BHCGM, Maraha B, Hollemans L, Sprong H, Brandenburg AH, Westenend PJ, Kusters JG. Evaluation of Borrelia real time PCR DNA targeting OspA, FlaB and 5S-23S IGS and Borrelia 16S rRNA-qPCR. Journal of Microbiological Methods (2014). http://doi.org/10.1016/j.mimet.2014.09.001.
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26. Berglund J, Stjernberg L, Ornstein K, Tykesson-Joelsson K, Walter H. 5-y follow-up study of patients with neuroborreliosis. Scand. J. Infect. Dis. 2002; 34(6): 421-425.
27. Berndtson K. Review of evidence for immune evasion and persistent infection in Lyme disease. Int J of General Medicine 2013; 6: 291-306. [Lyme disease spirochetes are adapted to persist in immune competent hosts; they are can remain infective despite aggressive antibiotic challenge.]
28. Bloom BJ, Wyckoff PM, Meissner HC, and Steere AC. Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infect. Dis. J. 1998; 17(3): 189-196.
29. Bradley JF, Johnson RC, Goodman JL (1994) The persistence of spirochetal nucleic acids in active Lyme arthritis. Ann Intern Med 120: 487-489.doi: 10.7326/0003-4819-120-6-199403150-00007 [human]
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31. Breier F, Khanakah G, Stanek G, Aberer E, Schmidt B, and Tappeiner G. Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Br J Dermatol 2001; 144: 387-392.
32. Bockenstedt LK, J Mao, E Hodzic, SW Barthold, and D Fish. Detection of attenuated, non-infectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. J Infect Dis 2002; 186: 1430-1437. [Bb persistence in mice]
33. Bockenstedt LK, Gonzalez DG, Hamberman AM, Belperron A (2012) Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 122: 2652-2660. doi: 10.1172/jci58813.
34. Breier F, Kkhkanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, and Tappeiner G. Isolation and polymerase chain reaction of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcereating bullous lichen sclerosus et atrophicus. Br J Dermatol 2001; 144: 387-392.
35. Brorson O and Brorson S-H. Transformation of cystic forms of Borrelia burgdorferi to normal mobile spirochetes. Infection. 1997; 25: 240-246. [change in physical characteristics; change of spirochetes to other pleomorphic forms, i.e., cell wall deficient forms, namely cysts.]
36. Brorson O and Brorson S. In vitro conversion of Borrelia burgdorferi to cystic forms in spinal fluid, and transformation to mobile spirochetes by incubation in BSK-H medium. Infection. 1998; 26: 144-150. [change in physical characteristics; change of spirochetes to other pleomorphic forms, i.e., cell wall deficient forms, namely cysts.]
37. Brorson O and Brorson SH. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to metronidazole. APMIS 1999; 107: 566-576.
38. Brorson O and Brorson SH. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole. International Microbiol 2004; 7: 139-142.
39. Brorson O and Brorson SH. An in vitro study of the activity of telithromycin against mobile and cystic forms of Borrelia afzelii. Infection 2006; 34: 26-28.
40. Brorson O Brorson SH, Scythes J, MacAllister J, Wier A, and Margulis L. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic tigecycline. Proc Natl Acad Sci USA 2009; 106: 18656-61
41. Brown JP, Zachary JF, Teuscher C, Weis JJ, and Wooten M. Dual role of interleukin-10 in murine Lyme disease: regulation of arthritis severity and host defense. Infect Immun 1999; 67: 5142-5150. [suppression of harmful immune responses: defense stratagem of burgdorferi]
42. Burrascano J. Failure of aggressive antibiotic therapy to protect the placenta from invasion by burgdorferi in a pregnant patient with Lyme borreliosis.  6^th Annual International Science Conference on Lyme Disease and other Tick-borne Diseases.1993.
43. Cabello FC, Godfrey HP, and Newman SA. Hidden in plain sight: Borrelia burgdorferi and the extracellular matrix. Trends in Microbiology 2007; 15: 350-354. [sequestration]
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45. Cadavid D, O’Neill T, Schaefer H, and Pachner AR. Localization of Borrelia burgdorferi in the nervous system and organs in a nonhuman primate model of Lyme disease. Lab Invest 2000; 80: 1043-1054.
46. Cadavid D, Y Bai, E Hodzic, K Narayan, SW Barthold, and Pachner AR. Cardiac involvement in non-human primates infected with the Lyme disease spirochete Borrelia burgdorferi. Lab Invest 2004; 84: 1439-1450. [in monkeys]
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48. Cameron D. Results from Lyme disease treatment trial. Columbia University/LDA Conference, Lyme & Other Tick-Borne Diseases: Emerging Tick-Borne Diseases. October 28, 2005; Philadelphia, Pennsylvania.
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Compiled by: John D. Scott, B.Sc. (Agr.), M.Sc.

08 August  2019                                                                                                                                                                                        Research Scientist (Acarology)

Governor General Medalist

Response to Proposed IDSA/AAN/ACR Guidelines, 2019

The IDSA/AAN/ACR guidelines give the illusion that Lyme disease is hard to catch, easy to diagnose, and easy to cure. The party-line message conveys the idea that Lyme disease is practically a non-issue. Any protean, clinical manifestations associated with Lyme disease that remain after 28-days of treatment are attributed to “medically-unexplained symptoms.” Of course, these “medically-unexplained symptoms” are vague, and never described or divulged. These guidelines take the stand that one size fits all.

“Medically-unexplained symptoms” is a bogus concept to justify a flawed belief. Persisting symptoms have a cause or physiological origin. Labelling ongoing symptoms as “unexplained” shows a lack of in-depth pathological research and, likewise, an unwillingness to find the real cause. By not recognizing persistence and co-infections, bias takes front and centre. Such symptoms are often unexamined rather than unexplained.

When a medical finding is incompatible with a hypothesis and diagnosis, then the hypothesis and diagnosis must be questioned. The IDSA/AAN/ACR Lyme disease guidelines have been defended by its authors by labelling the “unexplained medically symptoms” as subjective and, thereby, keeping the flawed belief system intact.

In addition, the IDSA/AAN/ACR guidelines reflect studies that are based on circular reasoning to substantiate outmoded dogma. This approach is no different than a card player stacking the deck before the game begins. Such tack is bogus science. For example, when all participants in a Lyme disease study are positive beforehand, this criterion inflates the results. The performance of serology testing in such a study may look marvellous on paper, but, in fact, it is substandard or mediocre when used in a commercial lab. Such inflated results may sell more test kits, but clients take the brunt. Poorly designed studies based on circular reasoning fail to gather the facts and, as a result, end up as flawed science. Lyme disease patients are shortchanged because of non-scientific methodology.

The draft IDSA/AAN/ACR guidelines for Lyme disease may or may not work well when an antibiotic is administered right after a known tick bite. For instance, some clinicians are using two antibiotic pills, whereas other health-care practitioners are using 4-6 weeks of antibiotics. There are multiple shortfalls in the complex dynamics of treating Lyme disease and associated tick-borne diseases. These shortcomings fail to incorporate a multitude of subtle factors, including persistence, co-infections, length of tick attachment, clinical manifestations, treatment failures, and alternate modes of transmission. 

Tick bite

The tick bite has been touted as the typical mode of transmission of the Lyme disease bacterium, Borrelia burgdorferisensulato (Bbsl); however, there are other known modes of transmission. Only 14% to 41% of Lyme disease patients remember a tick bite [1,2]. Therefore, basing treatment of Lyme disease on recall of a tick bite is a spurious way to diagnose and treat this zoonosis. Additionally, there is no set pattern on what pathogen any given tick is harbouring. For instance, the blacklegged tick, Ixodes scapularis, is known to carry and transmit at least 10 different tick-borne pathogens [3] To know what any tick is carrying at any given time is a quandary. Waiting for symptoms to develop after a tick bite is like playing Russian roulette with the future health of the patient. All tick bites should be treated as soon as possible.

Rash

Only 9% to 39% of Lyme disease patients have an erythema migrans (EM) rash [1,4,5]. Overall, there are at least 19 types of rashes associated with Lyme disease. Pathologically, the homogenous rash is more prevalent than the bull’s-eye rash, and >50% of Lyme disease patients have a homogeneous rash [4,6]. Atypical rashes have been reported [7-9]. Basing a diagnosis on whether the patient has had a rash is fraught with misinterpretation and, can potentially result in a misdiagnosis. Recurrent erythema migrans rashes may occur during and after antibiotic treatment [9]. Disappearance of an EM rash does not mean a cure of Lyme disease [10,11].

Length of tick attachment

The length of time a tick has been attached to a patient is most often miscalculated. Clinicians are notorious for telling patients that a tick has not been attached long enough for pathogens to be transmitted. Invariably, health-care practitioners will underestimate attachment time. They overlook the fact that Powassan virus can be transmitted in less than 15 minutes [12]. They also forget that Babesia sporozoites are present in the salivary tick glands andare transmitted promptly when the tick starts to feed [13]. Furthermore, Anaplasmaphagocytophilum (human anaplasmosis) can be transmitted in less than 24 hours [14]. Moreover, when tick salivary glands of I. scapularis ticks are infected with Bbsl, transmission can occur in less than 24 hours [15]. There is a disconnect between clinicians who guess how long ticks are attached and those who actually know how long they are attached. Clinicians are not acarologists, and have not studied tick engorgement and attachment times. Consequently, clinicians frequently misjudge the length of time a tick is attached. Such oversights can easily lead to not prescribing antimicrobials and, ultimately, to mismanagement and misdiagnosis.

Co-infections

When it comes to blacklegged ticks, Bbsl and Babesia are the most common co-infections followed closely by Bbsl and Bartonella spp. in the temperate zone of North America [1]. Potentially, I. scapularis may be infected with any combination of tick-borne pathogens, including Bbsl, Borrelia miyamotoi, Babesia spp., A. phagocytophilum, Bartonella spp., Deer tick virus (Powassan virus group), Mycoplasma spp., Francisellatularensis, Ehrlichiamuriseauclairensis, and HemocyticRickettsia-like organisms [3]. Fully engorged I. scapularis females can cause tick paralysis [16]. Other tick species have their own set of pathogens. For instance, lone star ticks, Amblyommaamericanum, have at least 6 tick-borne zoontic pathogens and, likewise, American dog ticks, Dermacentorvariabilis, have at least 3 tick-borne zoonotic pathogens [3]. Notably, fully engorged females of A. americanum and D. variabilis can also cause tick paralysis in humans [17].

Persistence

The persistence of Bbsl in the body is well documented. Bbsl is pleomorphic and has diverse forms (i.e., spirochete, spherocytes, blebs, granules) [18-20] and, collectively, biofilms [20,21]. Bbsl side-steps the human immune response and sequesters in deep-seated tissues (i.e., ligaments, tendons, bone, brain, eye, scar tissue, and glial and neuronal tissues). Since these areas of the body lack the ability to mount an immune response, Bbsl can sustain a high level of spirochetemia in perpetuity. Over the past 25 years, I have compiled a list of 348 peer-reviewed scientific articles showing persistence of Bbsl. Comprehensive studies abound [18,22-25]. See attached list on Bbsl persistence. For anyone to ignore this comprehensive persistence list is denying the facts about this stealth pathogen to persist in certain mammals, including humans.

Neurological and Psychiatric Manifestations

Once Bbsl becomes established in the brain and central nervous system, it causes a multitude of neurological and psychiatric manifestations. Bbsl can cause “brain fog,” memory loss, meningitis, encephalitis, neuroborreliosis, and perplexing psychiatric phenomena. Patients may have cognitive dysfunction, be excessively aggressive, suicidal, and homocidal [26-29]. The IDSA/AAN/ACR guidelines detour these serious clinical issues. As well, the guidelines by-pass symptoms relating to the hypothalmic-pituitary-adrenal axis that are linked to the parasympathetic nervous system and brought on by Lyme disease. Patients are often misdiagnosed with an idiopathic disease or medical condition. Lyme encephalitis is often labelled as a somatoform disorder, meaning “it’s all in the head.” The IDSA/AAN/ACR guidelines treat Lyme disease patients in a vacuum, rather that meeting an individual patient’s health needs.

Testing

The two-tier Lyme disease serology is fraught with low sensitivity. In a study by Fallon et al. (2014), it is noteworthy that the two-tier serology testing endorsed by the Centers for Disease Control and Prevention (CDC) had a sensitivity of only 48.6% for patients with persistent symptoms following standard Lyme disease treatment. These results were consistent with other findings [30]. In an effort to improve sensitivity, one “Specialty Lab X” used two strains of Bbsl (i.e., B31 and 297). At the same time, it also included the protein bands of 31 kDa (OspA) and 34 kDa (OspB) in the interpretation of Western blot results, thus raising the sensitivity to 89% [31]. Ultimately, these changes minimize any ambiguity with Lyme disease serology test. By using recombinant OspA and OspB, “Speciality Lab X” is able to raise the sensitivity even higher. In contrast, the two-tier Lyme disease serology testing is destined to being substandard, especially with advance cases of Lyme disease. Of upmost significance, the poor diagnostic accuracy of serological tests conducted early in the infection process has been noted very recently in the 2018 Report to Congress [32]. In essence, the IDSA/AAN/ACR guidelines have banked on a flawed, substandard testing system (i.e., two-tier Lyme disease serology testing) to state whether patients have or do not have Lyme disease.

False Negative Results

False negatives for Lyme disease patients with advanced clinical manifestations range in the neighbourhood of 50%. Biofilm busters that are used one month prior to blood draw and testing boost the immune response and, therefore, increase sensitivity. Misinterpretation of false negatives is exacerbated by clinicians who desire to automatically deny Lyme disease. In essence, the two-tier Lyme disease serology testing is woefully unreliable. This mode of testing must be seriously questioned, and alternate methods must be employed.

Chronic Lyme disease

The proposed IDSA/AAN/ACR guidelines fail to acknowledge the fact that chronic Lyme disease is a problematic issue for the majority of Lyme disease patients. Multiple articles report the persistence of Bbsl, and this phenomenon has become a huge challenge, especially for disabled Lyme disease patients [33]. Chronic Lyme disease has been defined [34].

Post Lyme disease treatment syndrome

The term, “post Lyme disease treatment syndrome,” has never been defined, and does not exist. Any symptoms after Lyme disease treatment has a cause whether it be another etiological microorganism or an ongoing Bbsl infection. Lyme disease has been well documented in the peer-reviewed medical literature to have the ability to cause a persistent, chronic infection. See attached list of Bbsl persistence.

Borrelia burgdorferisensulato transmitted by blood transfusion

Alternate modes of transmission of Bbsl have been reported in the human population. It is noteworthy that Bbsl can be transmitted by blood transfusion [35]. Using improved culturing methods, Sapi et al. have effectively cultured Bbsl from human blood with high proficiency [36]. Bbsl transmission via blood transfusion obviously is another potential mode of contracting Lyme disease.

 

Borrelia burgdorferisensulato transmitted by breast milk

Bbsl can be transmitted from the mother with Lyme disease to the newborn via breast milk. Breast milk from Bbsl-infected mothers has been shown to harbour spirochetes that can be detected by PCR and grown in culture [37]. Mothers are encouraged to breast feed, so that their newborns will receive colostrum to build a healthy immune system. However, both the mother and the infant must be carefully monitored and treated with antimicrobials to treat Bbsl and any relevant associated, tick-borne pathogens.

Rapid transmission of Borrelia burgdorferisensulato to the brain

The IDSA/AAN/ACR guidelines fail to recognize the rapid transmission of Bbsl to the brain. In a study with rats, Galbe et al. found that Bbsl invades vital organs shortly after intravenous inoculation of Bbsl spirochetes [38]. In a study using rats, the bladder and the kidneys were the primary sites of dissemination. The liver appeared to be directly involved in clearance of Bbsl spirochetes while the brain was invaded within 24 hours. The guidelines fail to recognize the rapid invasion of Bbsl into the brain. Bbsl persists in the brain because it does not mount an immune response [39].

Congenital Lyme disease

The IDSA/AAN/ACR guidelines side-steps transplacental transmission of Bbsl from mother to neonate as an alternate mode of transmission of Lyme disease [40-44]. Not only is transplacental transmission of Bbsl evident in humans, it is also present in other mammals, including horses, cows, dogs, mice, rats, and coyotes where spirochetemia was identified in offspring, often resulting in adverse outcomes [45-47].In utero transmission is a potential mode by which Bbsl spirochetes can be transmitted in a breeding population in the absence of a tick vector.

By using immunohistochemistry and monoclonal antibodies, researchers have documented that mothers who contract Lyme disease prior to pregnancy can transmit Bbsl to the fetus [48]. Additionally, by employing immunofluorescence, silver staining and culture, clinical research has found that mothers who were asymptomatic with no recollection of a tick bite and seronegative by standard Lyme disease serology, can transmit Bbsl to the fetus [41]. Ultimately, congenital Lyme disease can cause abortion, stillbirth, and infant death [49].

Furthermore, a German physician highlighted a 3-day-old infant with neonatal sepsis, and who had positive IgM and IgG Lyme disease serology and cerebral spinal fluid. The mother was asymptomatic and had no recollection of a tick bite [50]. Both mother and baby were negative for syphilis and mononucleosis. Although the mother was asymptomatic, the absence of clinical symptoms did not rule out spirochetosis of the fetus.

As well, a 1986 case report from Slovenia highlighted an asymptomatic mother with no recollection of a tick bite who delivered a 34-week-old stillborn female infant. Upon autopsy, dark-field microscopy examination of lung, liver and brain tissue specimens revealed spirochetes. The mother tested positive for Lyme disease and, using IFA testing, was negative for syphilis [51]. In another case report by Lavoie et al. [44], an initially healthy newborn was re-admitted at 8 days with lethargy, unresponsiveness, peripheral cyanosis, systemic hypertension, myocardial dysfunction and abdominal aortic thrombosis. The neonate died. Upon autopsy, Bbsl was cultured from the frontal cerebral cortex, and also identified in the heart and brain by silver staining. The mother was seronegative by standard Lyme disease serology with no recollection of a tick bite or EM rash and had non-specific symptoms. Unfortunately, the IDSA/AAN/ACR guidelines stumble over congenital Lyme disease.

Endemic Area

One of the IDSA/AAN/ACR criteria for having Lyme disease has depended on whether a patient has visited or lived in an endemic area. In reality, this criterion has been fraught with problems, and is potentially misleading. First, a patient may live in an endemic area and not know it; there is always a first for everything. In Ontario, there was thought to only be one hotspot (Long Point, Ontario) where there was a Lyme disease endemic area in Canada. Now, I have a list of 71 hotspots that have established populations of I. scapularis ticks in the province. Second, there has been little consideration given to the fact that migratory songbirds widely disperse Bbsl-infected ticks [52-59]. Neotropical and southern temperate songbirds can transport ticks from as far south as Brazil and transport them into Canada [60-62]. Therefore, people do not have to frequent an endemic area to contract Lyme disease. The IDSA/AAN/ACR criteria for visiting an endemic area turns out to eccentric. It may be helpful, but it can just as easily be off-base. Third, new findings reveal that more Lyme disease is contracted in the bedroom during intimate relationships than frequenting the outdoors [63,64]. Bbsl is a first cousin to syphilis, so contracting Lyme disease via intimate relationships isnot a great leap of faith. We see many intimate couples with Lyme disease.

Pharmacists Prescribing Antimicrobials

If pharmacist clinicians are going to prescribe antimicrobials, they must have pharmacists’ training certification, such as the Lyme disease physician training program by the International Lyme and Associated Diseases Society (ILADS) that specifically specializes in tick-borne, zoonotic diseases. Also, failure to recognize that any tick may be infected with piroplasms (e.g., Babesia divergens-like, Babesia duncani, Babesia microti, Babesia odocoilei) is playing with wildfire. Certain tick-borne pathogens do not respond to one- or two-pill treatments. Furthermore, certain brief treatments may not enter the brain.

Impact on the family

The IDSA/AAN/ACR guidelines do not address the devastating impact of chronic Lyme disease and the sociological fallout within families. Entire families are affected by Lyme disease often resulting in serious debilitating illness and complex, multisystem chronic infection. As well, there is nothing in the guidelines to counter the firestorm of rejection by schools, employers, churches, clubs, and organizations. The officials of these institutional bodies have an egregious response to absenteeism by sick Lyme disease patients.

Medical Boards and Licensing Colleges

There is no clear thought given to the denunciation by medical boards and medical licensing colleges that harass, victimize, and persecute health-care practitioners when they use long-term antimicrobials. As a result, these licensing bodies become “the elephant in the consultation room” and, thus, physicians and nurse practitioners are afraid to use guidelines that promote long-term antimicrobial treatments. These health-care practitioners are afraid they will be investigated and disciplined. As a result, patients’ lives are jeopardized and, in many cases,physically and mentallydestroyed.

Conclusion

With all the shortcomings in the proposed IDSA/AAN/ACR guidelines, this superficial proposal is destined to be another set of ill-founded, medical guidelines. As it would seem, medical professionals are out to dupe the public with illegitimate guidelines. As it stands, the treatment of Lyme disease and associated tick-borne, zoonotic diseases is based on cookie-cutter mentality generated by outmoded studies rather than designed to treat each individual patient as clinically required. The proposed guidelines are programmed to be problematic. This highly adaptive microorganism is here to stay in the environment.

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John D. Scott, B.Sc. (Agr.), M.Sc.

Research Scientist (Acarology)

E-mail: jkscott@bserv.com

Fergus, Ontario Canada

Attachment: Borrelia burgdorferisensulato persistence list (348 peer-reviewed scientific references).

General comments on entire draft, pages 2-69, lines 45-1605:

Throughout the 2019 draft revised guidelines, an overriding concern is the generation of false positive diagnoses and misattribution of symptoms to Lyme disease. In contrast, there is little, or no concern voiced about the possibility of false negative diagnoses and misattribution of Lyme disease symptoms to other etiologies. Obviously, all patients, whatever their ailment, should be accurately diagnosed in a timely manner.

Testing methods more sensitive and reliable than the CDC standard two-tier test (STTT), as concluded by 40 Lyme disease academic and government specialists attending a Banbury Conference at Cold Spring Harbor Laboratory, and a year later by the Tick-Borne Disease Working Group, are desperately needed to differentiate between those who do and those do not have Lyme disease. Individuals suffering from Lyme and other tick-borne diseases (TBDs) who are not promptly diagnosed are likely contributing, at least in part, to the accumulation of patients suffering from post-treatment Lyme disease syndrome(PTLDS).

Because of the severe consequences of missed or delayed diagnosis of Lyme disease, it is extremely important to minimize false negative diagnoses as well. Specific guidance on how best to avoid false negative diagnoses would be invaluable to medical care providers.

……To conclude, the content and bibliography of the 2019 revised IDSA guidelines fails to acknowledge evidence or reference published scientific and medical studies that could and should convey a more nuanced understanding of the complexities of Lyme disease diagnosis, symptomatology, treatment, and treatment failure. A more inclusive, open-minded, and informed approach to conveying information can only benefit the Lyme disease physician and patient community, as it will better serve to enhance co-operation, reduce controversies that divide the IDSA and ILADS ‘camps’, and ultimately reduce the likelihood of false negative and false positive diagnoses.

Tick bites, prevention, and prophylaxis of Lyme disease – What diagnostic tests should be used following tick bite?, pages 19-20, lines 453-467: It states, “We recommend against testing for B. burgdorferi in an Ixodes tick following a bite”. While true that the presence of a pathogen does not reliably predict the likelihood of clinical infection, there still is valuable information to be gained by testing ticks. Primary care physicians, even in Lyme-endemic areas, are not always familiar with the tick species common to a given location or the pathogen(s) they may carry. The stated rationale for the recommendation not to test is that “Even in areas that are highly endemic for Lyme disease, patients presenting with an Ixodes tick bite have a low probability of developing Lyme disease…”. This statement is not referenced and is unsupported by the fact that in highly endemic areas, in the northeastern U.S. in particular, the carriage rate for B. burgdorferi can be 50% or greater and such high carriage rates correlate with a higher incidence of Lyme disease. Tick removal and sending it for testing is a relatively rare event and thus should not contribute significantly to unnecessary antibiotic prescriptions. A major benefit to tick testing is that if no pathogens are found, this information would put the patient’s mind at ease.  If instead, the tick tests positive for one or more pathogens, this will focus the physician’s and patient’s attention on what symptoms to look for and better inform a treatment strategy if such symptoms arise.

The guidelines also suggest that “Anticipatory guidance is recommended so that a prompt diagnosis of Lyme disease (as well as other Ixodes tick transmitted infections) can be made should a patient develop symptoms”. However, given the inadequate familiarity most physicians have regarding ticks and tick-borne agents in their area, let alone in an area(s) to which a patient may have traveled and been bitten, there is no basis for thinking such anticipatory guidance can be provided. It is hard to rationalize why the guidelines would advocate for physicians and patients to make decisions having less rather than more information in hand, especially when the benefits of a prophylactic single dose of Doxycycline are substantial and the risks negligible.

Neurological Lyme disease – For which neurological presentations should patients be tested for Lyme disease?, page 36, lines 840-841:

It states that “In patients with cognitive decline the guidelines recommend against routine testing for Lyme disease.”

Global Lyme Alliance vehemently disagrees with this statement because it does not take into consideration the extensive evidence in peer-reviewed medical journals describing the cognitive decline experienced by Lyme neuroborreliosis patients. Such studies include patients with PTLDS, as defined by the IDSA-proposed case definition, who experience cognitive decline as well as PTLDS patients with neuropsychiatric symptoms linked to neuroimmune responses. This latter reference also argues against the guidelines’ claim that “No studies suggest a convincing causal association between Lyme disease and any specific psychiatric conditions”.

If patients present with otherwise unattributable cognitive decline, and they live in a Lyme-endemic area, why should a physician not consider Lyme disease in their differential diagnosis?

To not do so risks a missed/delayed diagnosis, and it is well-established that the earlier the treatment for Lyme disease is initiated the more positive the prognosis for recovery and cure. It also is recognized that cognitive symptoms can vary depending on a patient’s age, so a “one size fits all” statement that patients with (otherwise) unexplained cognitive decline should not be tested for Lyme disease seems at odds with a careful process of differential diagnosis and best-practice medical care.

Prolonged symptoms following treatment of Lyme disease, page 61, lines 1412-1419:

Reference is made to studies of “patients appropriately diagnosed and treated for Lyme disease” who describe either “persisting or recurrent fatigue, musculoskeletal pain, neurocognitive and other non-specific subjective symptoms”.

These are in fact patients clinically defined by Rebman et al. as having PTLDS and yet reference to this seminal study and specific mention of this PTLDS patient population is missing and should be included in the body and bibliography of the guidelines. In this same section it states that long-term “symptoms appear to subside over time…”.

For patients suffering from PTLDS, most continue to have debilitating symptoms. In fact, a Dutch study found an average of 1.7 disability-adjusted life years lost due to persisting symptoms attributable to Lyme, and even longer for some patients.

Prolonged symptoms following treatment of Lyme disease – Chronic Lyme disease, page 64, lines 1474-1479: It states that “The term ‘chronic Lyme disease’ as currently used lacks an accepted definition for either clinical use or scientific study, and it has not been widely accepted by the medical or scientific community”.

Although this statement is correct with respect to the lack of an accepted clinical definition, at least 68 publications in peer-reviewed scientific and medical journals spanning 1985 to 2019 describe the chronic infectious and persistent nature of Lyme disease.

While treatment of patients with Doxycycline or other standard-of-care antibiotics is quite effective when provided within the first few weeks of infection, no clinical studies have demonstrated complete clearance of spirochetes; just elimination of symptoms for some, but not all patients (i.e., PTLDS patients). When early treatment is ineffective or initial diagnosis is delayed, B. burgdorferi can avoid pharmaceutical and/or immune clearance and spirochetes have an opportunity to disseminate and cause persistent disease. Literally a dozen or more bacterial pathogens are capable of establishing persistent infection and associated chronic disease. It would be truly remarkable if B. burgdorferi were unable to do the same. To our knowledge, there is no scientific or medical evidence to suggest they are incapable. Whether persistent disease is synonymous with persistent infection is an important scientific question worthy of objective consideration and further careful investigation, rather than recrimination, disparagement and dismissal. The revised guidelines would stand on firmer scientific/medical footing were it to acknowledge that the question of persistent disease vs. infection is still an open question, rather than suggesting the latter has no evidentiary support whatsoever.