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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59. Scott, J.D.; Durden, L.A. New records of the Lyme disease bacterium in ticks collected from songbirds in central and eastern Canada. J. Acarol. 2015, 41, 241–249.
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61. Scott, J.D.; Durden, L.A. Amblyommadissimile Koch (Acari: Ixodidae) parasitizes bird captured in Canada. Appl. Acarol. 2015, 20, 854–860.
62. Scott, J.D.; Durden, L.A. First record of Amblyommarotundatum tick (Acari: Ixodidae) parasitizing a bird collected in Canada. Appl. Acarol. 2015, 20, 155–161.
63. Middelveen, M.J.; Sapi, E.; Burke, J.; Filush, K.R.; Franco, A.; Fesler, M.C.; Stricker, R.B. Persistent Borrelia infection in patients with ongoing symptoms of Lyme disease. Healthcare2018, 6, 33.
64. Fesler, M.C.; Middelveen, M.J.; Burke, J.M.; Stricker, R.B. Erosive vulvovaginitis associated with Borrelia burgdorferi J. Investig. Med. High Impact Case Rep. 2019,7, 2324709619842901.

 

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).