Stakehold

parties the development of guidance for clinicians on dealing with the disaffected group

with un-provable Lyme disease. This will cover the therapeutic approach, investigation of

cases and disengagement strategies when further investigation is counter-productive.”

In view of their plans for ‘development of guidance for clinicians’, one may speculate that

PHE will attempt to steer the NICE GDG process to meet their predetermined agenda.

That agenda appears to include a 6 month period after which they deem it acceptable for

doctors to ‘disengage’ from patients if the patient cannot ‘prove’ that they Lyme borreliosis.

This agenda could deprive patients of medical care and deny them treatment and could be

attractive to some who are more concerned about financial costs than patient welfare.

The strategy might also be favourable to medical re-insurance companies who have saved

a lot of money thanks to a few psychiatrists who compounded the neurological disease,

Myalgic Encephalomyelitis with ‘CFS’ and then classified CFS as a Functional Somatic

Disorder. This has meant that policy claims can be limited to 2 years for a notoriously

chronic and severely debilitating neurological disease. Are people with chronic Lyme

borreliosis destined for the same?

'Professor Sir Simon Wessely's group' are psychiatrists, and it seems that PHE would like

them to take control of the fate of patients who do not recover in an allotted time. They

have some history with NICE, as observed by Professor Malcolm Hooper (2007) in his

written evidence to the Parliamentary Select Committee on Health regarding the NICE

GDG for ‘CFS/ME’:

“14. The advisors upon whom NICE relies have been shown to have undeclared vested

interests: These psychiatrists and their adherents are heavily involved with the medical

insurance industry, including UNUM Provident, Swiss Life, Canada Life, Norwich Union,

Allied Dunbar, Sun Alliance, Skandia, Zurich Life and Permanent Insurance, as well as the

re-insurers Swiss Re...”

Dr Darrel Ho-Yen (1990), who became the head of the Lyme Reference Laboratory at

Inverness, commented on the Wessely group’s ideas in the Journal of the Royal College of

General Practitioners: “…it has been suggested that a new approach to the treatment of

patients with postviral fatigue syndrome would be the adoption of a cognitive behavioural

model (Wessely S, David A, Butler S, Chalder T: Management of chronic (postviral) fatigue

syndrome. JRCGP 1989:39:26-29). Those who are chronically ill have recognised the folly

of the approach and, far from being maladaptive, their behaviour shows that they have

insight into their illness”.

VIRAS rejects the concept of a 6 month period for the transformation of a patient’s LB

infection from one stage to another as inaccurate, negligent and unethical. We are curious

to know where this idea originated and what scientific justification was provided for this

notion of an infectious disease progressing according to a calendar.

References

CDC/Fukuda. 1994. Guidelines for the Evaluation and Study of CFS. Centres for

Disease Control and Prevention. http://www.cdc.gov/cfs/case-definition/1994.html

Health and Safety Executive (2012). Lyme disease and services in the HPA. Advisory

Committee on Dangerous Pathogens (ACDP) - ACDP/99/P62.

http://www.hse.gov.uk/aboutus/meetings/committees/acdp/161012/acdp_99_p62.pdf

Hjetland R1, Nilsen RM, Grude N, Ulvestad E. 2014. Seroprevalence of antibodies to

Borrelia burgdorferi sensu lato in healthy adults from western Norway: risk factors and

methodological aspects. APMIS. 2014 Nov;122(11):1114-24. doi: 10.1111/apm.12267.

http://www.ncbi.nlm.nih.gov/pubmed/24730472

Hooper, Malcolm. 2007. Evidence submitted by Professor Malcolm Hooper (NICE 07).

Select Committee on Health.

http://www.publications.parliament.uk/pa/cm200607/cmselect/cmhealth/503/503we79.htm

ILADS (International Lyme and Associated Diseases Society). 2012. Peer Reviewed

Evidence of Persistence of Lyme Disease Spirochete Borrelia burgdorferi and Tick-Borne

Diseases. http://www.ilads.org/ilads_news/wp-

content/uploads/2015/09/EvidenceofPersistence-V2.pdf

Miklossy J. 2012. Chronic or late lyme neuroborreliosis: analysis of evidence compared to

chronic or late neurosyphilis. The Open Neurology Journal. 2012;6:146–157. doi:

10.2174/1874205X01206010146. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551238/

Mygland A, Skarpaas T, Ljøstad U. (2006). Chronic polyneuropathy and Lyme disease.

Eur J Neurol. 2006 Nov;13(11):1213-5. http://www.ncbi.nlm.nih.gov/pubmed/17038034

NHS Choices. 2014. Syphilis.

http://www.nhs.uk/Conditions/Syphilis/Pages/Symptomspg.aspx

Public Health England. 2015. Lyme disease: diagnosis and treatment.

https://www.gov.uk/government/publications/lyme-disease-diagnosis-and-treatment/lyme-

disease-diagnosis-and-treatment

Under Our Skin. 2007. LYME DISCOVERER WILLY BURGDORFER BREAKS SILENCE

ON HEATED CONTROVERSY 2007. Online: http://underourskin.com/news/lyme-

discoverer-willy-burgdorfer-breaks-silence-heated-controversy

U.S. Library of Medicine, MedlinePlus. 2015. Lyme Disease.

https://www.nlm.nih.gov/medlineplus/ency/article/001319.htm

West, Stirling. 2014. Rheumatology Secrets. Elsevier Health Sciences. Mosbey. 3rd

edition. ISBN-13: 978-0323037006.

Thank you for your comment on the issue of the classification of early and late Lyme disease as described in the consultation version of the scope. We have invited stakeholders to provide comment on this in a specific question at consultation to ensure that we collected the widest views on this issue. We now propose to present the guideline committee with the stakeholder feedback on this issue to allow them to determine the best approach for the guideline to take. As such, we have removed the detail linked to the definitions of early and late Lyme disease from the final scope. .
VIRAS Vector- borne Infection, Research – Analysis - Strategy	DQ5		Diagnostic Testing for Lyme Disease Diagnosis of Lyme borreliosis infections by indirect methods, i.e. looking for certain antibodies in patients’ blood, has been proved to be unreliable by many studies published over the past 3 decades. The criteria necessary for providing accurate clinical decision- making and for the safe stewardship of maintaining Public Health have not been met. A recently published meta-analysis by Leeflang et al., (1), reviews all testing methods to date and shows that this problem is evident: "We found no evidence that ELISAs have a higher or lower accuracy than immunoblots; neither did we find evidence that two-tiered approaches have a better performance than single tests. “However, the data in this review do not provide sufficient evidence to make inferences about the value of the tests for clinical practice. Valid estimates of sensitivity and specificity for the tests as used in practice require well-designed cross-sectional studies, done in the relevant clinical patient populations. “Furthermore, information is needed about the prevalence of Lyme borreliosis among those tested for it and the clinical consequences of a negative or positive test result. The latter depend on the place of the test in the clinical pathway and the clinical decisions that are driven by the test results or not. Future research should primarily focus on more targeted clinical validations of these tests and research into appropriate use of these tests." It should be realised that all of the validity data sets for test kits, as published by their manufacturers, have been determined in patients with known or highly probable borreliosis infection, as seen from their symptoms, such as EM rash, or frank symptoms such as facial palsy or Bannwarth’s syndrome. Rarely have any antibody tests been matched against true microbiological evidence, which would have had to have been done by checking each patient with a culture test. The test kits have not been validated in patients who have less obvious presentations of Lyme borreliosis. The only true validation would be to test each patient with manufacturer’s kits and then to assess each patient by means of culture and/or DNA detection of the bacteria. It is of the utmost clinical importance that the true state of the infection in each patient should be accurately assessed, This should be done in microbiological terms by looking for evidence of the bacteria themselves, instead of looking for the immune response. There are many reasons why the immune response is variable and often suppressed in patients with Lyme borreliosis. (2) Microscopic visualization of live Borrelia spirochetes offers the strongest of all proofs that an infection is present. Borrelia burgdorferi can be visualized directly in infected vectors, reservoir hosts, laboratory animals and clinical specimens from patients with Lyme borreliosis using dark-field or phase-contrast microscopy. The spirochetes may also be microscopically visualized after Giemsa, Gram, immunological or silver staining of specimens The BIA have dismissed microscopy and culture investigations of patients. They cite the long time period necessary for the borrelia spirochetes to grow, and the cost of technical manpower. However, if we are on the brink of a public health hazard, liable to affect future generations - because of the high probability of congenital transfer of the infection, and possible contamination of the nation’s blood supply - then the cost has to be met. In fact, costs will not be as high as expected, since advanced culture methods have recently been patented which enable identification of borrelia species in patient sera within 1 week, in many cases: This advanced culture method has been in operation as a successful commercial enterprise in Pennsylvania, at Advanced Laboratory Services, for the last 3 years, and has been published in the peer-reviewed literature (3, 4) and patented (5). The method is endorsed by Philip M. Tierno, Jr., PhD Frm Director of Clinical Microbiology and Immunology, New York University School of Medicine Dr Tierno refutes accusations by some CDC scientists that there might have been contamination during the method. (6). Criticism of the method by UK scientists has been quashed with research by Dr Sheila Woods and her team at Advanced labs. PHE have claimed that the spirochaetes seen in the microscope were artefacts, or pieces of collagen or fibrin. Sheila Wood used a special Rhodium-based stain which has the property of only attaching to collagen and fibrin, and it was conclusively shown that, in the very small percentage of cases where the obvious shape of Borrelia spirochaetes was not so distinct (about 2% of samples), the Rhodium stain did not attach to what were suspected to be Borrelia spirochaetes. The Rhodium stain did attach to bits of the background extra-cellular matrix, as it is designed to do, but absolutely did not stain the Borrelia. (7). The Abstract states : "In order to distinctly differentiate the organisms from the collagen of this matrix that could be observed as background in the staining process, we developed an immunostaining procedure using polyclonal and monoclonal antibodies in combination with rhodamine fibronectin. The culture samples from both control organisms and patient samples were tested using the new immunostaining protocol. Results showed clear delineation of organisms compared to the collagen pieces gathered in the harvesting process. This new immunostaining process, used with in vitro cultivation, provides for precise identification of cultured organisms." Given that the true prevalence of borreliosis in the UK has not been fully monitored, and that it will be bound to increase in the British Isles, as it has been seen to do so across the Northern hemisphere , we can expect tens of thousands of cases each year (8,9). The Health and Safety of the UK over the next 10 to 15 years will depend on how the NICE committee decides to tackle the problem of not just Lyme disease, but also other arthropod-borne infections. It is imperative that our health service chooses the best diagnostic techniques . References 1)The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis Leeflang et al. BMC Infectious Diseases (2016) 16:140. DOI 10.1186/s12879-016-1468-4 2) http://www.ilads.org/ly…/primary-care-physician-brochure.pdf 3) Improved Culture Conditions for the Growth and Detection of Borrelia from Human Serum. Sapi E, Pabbati N, Datar A, Davies EM, Rattelle A, Kuo BA. Int J M.5698. ed Sci 2013; 10(4):362-376. doi:10.7150/ijms 4)Assessment of New Culture Method to Detect Borrelia species in Serum of Lyme Disease Patients”. B. Johnson, Mark A. Pilgard, and Theresa M. Russell J. Clin. Microbiol. doi:10.1128/JCM.01674-13 5) http://advanced-lab.com/news/borrelia_culture_patent.pdf 6). http://www.advanced-lab.com/news/comment-lyme-tierno.pdf 7) Differentiation of Borrelia Microbes from Collagen Debris and Collagen Fibrils in Blood Cultures. J. Microbiology & Experimentation Volume 2 Issue 1. January 02, 2015 Sheila Wood, Akshita Datar, Namrata Pabbat, Divya Burugu and Amy Rattelle J. Microbiology & Experimentation Volume 2 Issue 1. January 02, 2015 S http://medcraveonline.com/JMEN/JMEN-02-00033.pdf 8) http://www.nhs.uk/…/Concern-about-rise-in-UK-Lyme-disease-c… and http://www.bristol.ac.uk/n…/2015/april/big-tick-project.html 9) An estimate of Lyme borreliosis incidence in Western Europe Robert A. Sykes, Phoebe Makiello Journal of Public Health | pp. 1 –8 | doi:10.1093/pubmed/fdw017	Thank you for your response and detailed comments on our questions. We will bring the detail of your response to the Guideline Committee's attention. The information will be used to inform the Committee's decision making as they develop the review protocols that guide the searches for and review of the evidence for the questions outlined in the guideline scope.
VIRAS Vector- borne Infection, Research – Analysis - Strategy	Gener al	Gen eral	VIRAS response to NICE request for comments on: “4) The inclusion of the following strains of Lyme Borreliosis for consideration as part of our review of the evidence: B. burgdorferi (and the subtype B. burgdorferi sensu stricto), B. garinii, B. afzelii” Borrelia Species causing Lyme borreliosis and Travel Risks Key Points  Since the discovery of borrelia burgdorferi in 1982, more species and strains have been discovered and implicated in Lyme borreliosis (LB)  As recently as 2016, the CDC and Mayo Clinic have announced a new LB species  As recently as 2016 Rudenko et al (14) provide evidence of the involvement of B. bissettii in human Lyme borreliosis  Regions endemic for LB species have expanded and are expected to continue to do so  A high number of UK residents travel abroad with increased risk of exposure to a greater range of LB species and strains The species of borrelia specific for ‘Lyme Disease’ were b. burgdorferi s.s., b. garinii and b. afzelii. This artificial restriction has long been discarded by scientists and physicians to recognise additional borrelia species responsible for ‘Lyme Borreliosis’ (LB). All authorities recognise LB as a growing threat. The World Health Organization Europe report on Lyme Borreliosis and Global Warming states (1): “Since the 1980s, tick vectors have increased in density and spread into higher latitudes and altitudes in Europe. It can be concluded that future climate change in Europe will facilitate a spread of LB into higher latitudes and altitudes, and contribute to increased disease occurrence in endemic areas.” To meet this challenge, the Guidelines must recognise that non-endemic species could spread to the UK and accept the possibility of further unknown species and strains yet to be discovered. In Scientific American’s guest blog, Lyme Time Is upon Us Again. Pfiefer (2016)(2) remarks on Ixodes ricinus, (castor bean tick) which transmits LB in Europe: “In Europe, disease-ridden castor bean ticks, a relative of those in the U.S., are on the move too, spreading 300 miles north in Sweden and Norway to latitudes that were considered too cold only a generation ago. Prolific and resilient, they are even scaling mountains, climbing 1,300 feet up the Dinaric Alps of Bosnia and Herzegovina and moving to new heights in the Czech Republic and Scotland.” LB species causing disease in Europe include: burgdorferi, afzelii, garinii, spielmanii, lusitaniae, valaisiana, bisettii (Heyman et al. 2010)(3). Rizzoli et al state in Eurosurviellance (4): “LB is likely to become an increasingly relevant health risk in the near future due to complex interactions between diverse environmental and socio-economic factors, which will affect various aspects of disease ecology and epidemiology”. Risk to UK Residents Travelling Abroad Worldwide species of Lyme borreliosis spirochaetes pose a threat to UK residents travelling abroad. The CDC (2015)(5) state that LB in Europe is: “endemic from southern Scandinavia into the northern Mediterranean countries of Italy, Spain, and Greece andeastward from the British Isles into central Russia.” According to the UK Government, British nationals make millions of visits abroad each year. This increases the risk of exposure to Lyme borreliosis and a greater diversity of LB species and strains. Destination / Number of visits / (LB incidence per 100k pop) France 17 million 44 Germany 2 million 261 Netherlands 1.8 million 149 Austria 774,000 300 Switzerland 710,000 30 Sweden (Southern) 664,000 464 Czech Republic 300,000 38 Slovenia 100,000 155 UK reported incidence of LB per 100k pop: Scotland 5.9 England and Wales 1.73 (Source for travel abroad: https://www.gov.uk/foreign-travel-advice/france [change country name for other destinations in lowercase]) (Sources for incidence figures: see below) According to the Office for National Statistics (6) 62% of travel abroad by UK residents is for a holiday and 11% for visits to friends and relatives and might therefore be expected to be of at least several days. Therefore each year there are millions of visits by British nationals to other European countries where LB incidence ranges from 17 to 268 times the ‘official’ rate in England and Wales. Notwithstanding UK incidence figures which appear to be absurdly low, the high numbers travelling abroad are subject to a significant risk of exposure to diverse species and strains of borrelia. Pfiefer (2016)(7) observes: “In the Netherlands, rates of people diagnosed with the telltale Lyme rash ranged up to 514 per 100,000 in 2014. In areas of Germany and Sweden, studies of patient records found Lyme rates of 261 to 464 per 100,000. In Europe, the highest national rate—315 per 100,000 in 2009 – has been reported in Slovenia, one of few countries to aggressively track cases.” Travel to the USA UK residents make over 3 million visits to the USA each year (6). The CDC (2013)(8)