Stakehold

and clearly highlights the urgent need for prevention.” ’

Kiersten et al (2015)(9) state, “Over time, the number of counties in the northeastern states

identified as having high incidence of Lyme disease increased >320%: from 43 (1993–

1997) to 90 (1998–2002) to 130 (2003–2007) to 182 (2008–2012).” Their map

(http://wwwnc.cdc.gov/eid/article/21/8/14-1878-f1) documents the exponential spread of LB

over vast areas, graphically illustrating the growing threat of LB to more regions and more

people.

Pfiefer (2016) (10) remarks on Ixodes scapularis, the ‘deer tick’ which transmits LB in North

America: “In 1996, Ixodes scapularis, as it is known, had planted a foothold in 396

American counties. By 2015, the tick was established in 842 counties. This does not count

another 578 counties—in all nearly half the continental U.S. total—in which the tick has

been officially “documented.” ”

Borrelia species with known or suspected potential to cause LB

Borrelia Mayonii

The Centres for Disease Control and Prevention, 2016, describe a “New Lyme-disease-

causing bacteria species discovered. Borrelia mayonii closely related to B. burgdorferi.

“[]. Until now, Borrelia burgdorferi was the only species believed to cause Lyme disease in

North America.

“Scientists at the Mayo Clinic in Rochester, Minnesota, first suspected the possibility of

new bacteria after lab tests from six people with suspected Lyme disease produced

unusual results, according to the findings published today in Lancet Infectious Diseases.

Additional genetic testing at the Mayo Clinic and CDC found that the bacteria, provisionally

named Borrelia mayonii, is closely related to B. burgdorferi.

“This discovery adds another important piece of information to the complex picture of

tickborne diseases in the United States,” said Dr. Jeannine Petersen, microbiologist at the

Centers for Disease Control and Prevention.”(11)

Borrelia Bavariensis

Margos et al (2013) (12), state that Borrelia bavariensis is widely distributed in Europe and

Asia: “Since the original description of Borrelia bavariensis sp. nov. in 2009, additional

samples available from humans and ticks from Europe and Mongolia, respectively, have

been used to further characterize Borrelia strains belonging to this group of spirochaetes

that utilize rodents as reservoir hosts. These investigations suggested the presence of

related strains in Europe and Asia and confirmed their status as representing a distinct

species.”

Borrelia spielmanii

Maraspin, Ruzic-Sabljic and Strle (2014)(13) conclude in their case report:

“Our results corroborate previous findings that B. spielmanii is a cause of LB in Europe.

Thus, in addition to the Netherlands (2), Germany (10), and Hungary (1), LB caused by B.

spielmanii is also present in Slovenia.”

Borrelia Bissettii

Rudenko et al (2016)(14) report on, “the first recovery of live B. burgdorferi sensu stricto

from residents of southeastern USA and the first successful cultivation of live Borrelia

bissettii-like strain from residents of North America. Our results support the fact that B.

bissettii is responsible for human Lyme borreliosis worldwide along with B. burgdorferi s.s.

The involvement of new spirochaete species in Lyme borreliosis changes the

understanding and recognition of clinical manifestations of this disease.”

Borrelia lusitaniae

While B. lusitaniae is distributed throughout countries in Europe and North Africa, it is

believed to be the sole species of the Lyme borreliosis group in southern Portugal. Lizards

of the family Lacertidae are thought to be important reservoir hosts of B. lusitaniae.(15)

De Carvalho et al(2008)(16) remark:

“We have described a vasculitis-like syndrome associated with the isolation of B.

lusitaniae. Although the clinical presentation is not typical of Lyme borreliosis, this case

had features suggestive of vasculitis, which has been described as one of the

characteristic physiopathological aspects of this disease”

Borrelia Valaisiana

Diza et al (2004)(17) state:

“We detected B. valaisiana DNA in CSF of a patient with slow progressive spastic

paraparesis, which suggests that this microorganism might be the causative agent of the

disease. Nucleotide sequence information of Borrelia strains from clinical cases and ticks

from different countries will elucidate the molecular epidemiology of the disease.”

“The pathogenic capabilities of B. valaisiana are still uncertain; it has been detected by

PCR and restriction fragment length polymorphism analysis in skin biopsy specimens from

two erythema migrans patients and from patients with mixed infection (erythema migrans

and acrodermatitis chronica atrophicans) (4). Indirect evidence suggests that B. valaisiana

is involved in some chronic clinical manifestations (8).”

Reference 8 above is: Ryfell, et al (1999)(18), which states:

“Our results suggest an organotropism of Borrelia species and provide some evidence of a

pathogenic potential ofB. Valaisiana in humans.”

Schwab et al, (2013)(19) state in Borrelia valaisiana Resist Complement-Mediated Killing

Independently of the Recruitment of Immune Regulators and Inactivation of Complement

Components:

“In conclusion, we demonstrated that B. valaisiana isolates differ in their susceptibility to

human serum, thus providing some evidence that in particular serum-resistant isolates

might cause Lyme disease. Contrary to our expectations, certain B. valaisiana isolates

appear to possess different molecular mechanism(s) to inhibit complement activation,

independently of the recruitment of complement regulators or by inactivation of central

complement components. Even though that we are currently unable to decipher the

precise molecular mechanism, it is tempting to speculate that B. valaisiana ZWU3 Ny3

expresses an outer surface protein that directly interacts with components of the

complement system to inhibit complement activation. Further investigation is required to

identify potential complement inhibitory protein(s) of this particular borrelial strain.”

Cooper et al, (2001)(20) tested 75 ticks taken from wild animals in SW England. 41%

tested positive for the presence of borrelia DNA. 34% of these were also positive for

Borrelia valaisiana, considerably more than double the prevalence of this species in the

rest of Europe.

Conclusion

In view of the spreading areas endemic for Lyme borreliosis and the diversity of borrelia

species which pose a threat to humans; restricting Lyme borreliosis to just 3 of those

species would inevitably fail to protect UK residents.

Sources for Lyme Borreliosis Incidence in Europe:

Austria, 2005, Elisabet Lindgren, Thomas G.T. Jaenson. 2006. Lyme borreliosis in Europe:

influences of climate and climate change, epidemiology, ecology and adaptation

measures. World Health Organization Europe.

http://www.euro.who.int/__data/assets/pdf_file/0006/96819/E89522.pdf

Belgium , 2009, K. Vanthomme & N. Bossuyt & N. Boffin & V. Van Casteren. 2012.

Incidence and management of presumption of Lyme borreliosis in Belgium: recent data

from the sentinel network of general practitioners. Eur J Clin Microbiol Infect Dis (2012)

31:2385–2390. DOI 10.1007/s10096-012-1580-3 [figures referenced relate to confirmed

EM rash]

Czech Republic, 2005-14, Czech Republic 38/100k (Avg 2005-14). Ministry of Health.

State Health Institute. Selected Infectious Diseases in the Czech Republic in the years

2005-2014. http://www.szu.cz/modules/makepdf/make.php?id=1346

England and Wales, 2011, Public Health England.

https://www.gov.uk/government/publications/lyme-borreliosis-epidemiology/lyme-

borreliosis-epidemiology-and-surveillance

France , 2012, A Vandenesch, C Turbelin, E Couturier, C Arena, B Jaulhac, E Ferquel, V

Choumet, C Saugeon, E Coffinieres, T Blanchon, V Vaillant, T Hanslik. 2015., RIVM

(2015). INCIDENCE AND HOSPITALISATION RATES OF LYME BORRELIOSIS,

FRANCE, 2004 TO 2012. Eurosurveillance, Volume 19, Issue 34, 28 August 2014.

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20883

Germany, 2008, I. Müller, M. H. Freitag, G. Poggensee, E. Scharnetzky, E. Straube,

Ch. Schoerner, 1H. Hlobil, H.-J. Hagedorn, G. Stanek, A. Schubert-Unkmeir,

Norris, J. Gensichen, and K.-P. Hunfeld. Evaluating Frequency, Diagnostic Quality, and

Cost of Lyme Borreliosis Testing in Germany: A Retrospective Model Analysis. Clin Dev

Immunol. 2012; 2012: 595427. PMCID: PMC3254124. Published online 2011 Dec 27. doi:

10.1155/2012/595427

Netherlands, 2011, Coumou J1, van der Poll T, Speelman P, Hovius JW. Tired of Lyme

borreliosis. Lyme borreliosis in the Netherlands. Neth J Med. 2011 Mar;69(3):101-11.

http://www.ncbi.nlm.nih.gov/pubmed/21444934

Scotland, 2013, NHS Scotland http://www.documents.hps.scot.nhs.uk/giz/10-year-

tables/lyme.pdf

Slovenia, 2006, See 2.

Switzerland, 2005, See 2.

References

1. Elisabet Lindgren Thomas G.T. Jaenson. 2006. Lyme borreliosis in Europe: influences

of climate and climate change, epidemiology, ecology and adaptation measures.

World Health Organization Europe.

http://www.euro.who.int/__data/assets/pdf_file/0006/96819/E89522.pdf

2. Pfeiffer, Mary Beth. 2016. Scientific American. Guest blog, Lyme Time Is upon Us

Again. April 5, 2016. http://blogs.scientificamerican.com/guest-blog/lyme-time-is-upon-

us-again/

3 Heyman, Paul. Christel Cochez, Agnetha Hofhuis, Joke van der Giessen, Hein

Sprong, Sarah Rebecca Porter, Bertrand Lossone, Claude Saegerman, Oliver

Donoso-Mantke, Matthias Niedrig & Anna Papa. 2010. A clear and present danger:

tick-borne diseases in Europe. Expert Review of Anti-infective Therapy. Volume 8,

Issue 1, 2010. http://www.tandfonline.com/doi/full/10.1586/eri.09.118

4 A Rizzoli, H C Hauffe, G Carpi, G I Vourc’h, M Neteler, R Rosà. 2011. LYME

BORRELIOSIS IN EUROPE. Eurosurveillance, Volume 16, Issue 27, 07 July 2011.

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19906

5 CDC. 2015. Travel Health & the Yellow Book.

http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-

travel/lyme-disease

6 Office for National Statistics. 2014. Travel trends 2014.

http://www.ons.gov.uk/peoplepopulationandcommunity/leisureandtourism/articles/trav

eltrends/2015-05-20#uk-residents-visits-abroad

7 Pfeiffer, Mary Beth. 2016. See 2

8 CDC. 2013. CDC provides estimate of Americans diagnosed with Lyme disease each

year. August 19, 2013. http://www.cdc.gov/media/releases/2013/p0819-lyme-

disease.html

9 Kiersten J. Kugeler, Grace M. Farley,Joseph D. Forrester, Paul S. Mead. 2015.

Geographic Distribution and Expansion of Human Lyme Disease, United States. CDC.

Emerging Infectious Diseases. Vol. 21, No. 8, August 2015.

http://wwwnc.cdc.gov/eid/article/21/8/pdfs/14-1878.pdf

10 Pfeiffer, Mary Beth. 2016. See 2

11 Centres for Disease Control and Prevention. 2016. New Lyme-disease-causing

bacteria species discovered. Borrelia mayonii closely related to B. burgdorferi.

http://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html

12 Margos G1, Wilske B, Sing A, Hizo-Teufel C, Cao WC, Chu C, Scholz H, Straubinger

RK, Fingerle V. Borrelia bavariensis sp. nov. is widely distributed in Europe and Asia.

Int J Syst Evol Microbiol. 2013 Nov;63(Pt 11):4284-8)

13 Vera Maraspin, Eva Ruzic-Sabljic, and Franc Strle. 2006. Lyme Borreliosis and

Borrelia spielmanii. Emerg Infect Dis. 2006 Jul; 12(7): 1177

14 Rudenko N., Golovchenko M., Vancova M., Clark K., Grubhoffer L., Oliver J.H. 2016

Isolation of live Borrelia burgdorferi sensu lato spirochaetes from patients with

undefined disorders and symptoms not typical for Lyme borreliosis. Citation: Clinical

Microbiology and Infection, March 2016, vol./is. 22/3(267.e9-267.e15), 1198-

743X;1469-0691 (01 Mar 2016)

15 Vitorino, Liliana R. , Gabriele Margos, Edward J. Feil, Margarida Collares-Pereira,

Libia Zé-Zé, Klaus Kurtenbach. 2008. Fine-Scale Phylogeographic Structure of

Borrelia lusitaniae Revealed by Multilocus Sequence Typing. PlosOne. December

23, 2008. http://dx.doi.org/10.1371/journal.pone.0004002

16 Lopes de Carvalho & J. E. Fonseca & J. G. Marques & A. Ullmann & A. Hojgaard & N.

Zeidner & M. S. Núncio. 2008. Vasculitis-like syndrome associated with Borrelia

lusitaniae infection. Clin Rheumatol. DOI 10.1007/s10067-008-1012-z.

http://www.ncbi.nlm.nih.gov/pubmed/18795392

17 Diza, Eudoxia, Anna Papa, Eleni Vezyri, Stefanos Tsounis, Ioannis Milonas, and

Antonis Antoniadis. 2004. Borrelia valaisiana in Cerebrospinal Fluid. Emerg Infect Dis.

2004 Sep; 10(9): 1692–1693. doi: 10.3201/eid1009.030439. PMCID: PMC3320289.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320289/.

18 Ryffel, Karine; Olivier Péter, Bernard Rutti, André Suard, Eric Dayer. 1999. Scored

Antibody Reactivity Determined by Immunoblotting Shows an Association between

Clinical Manifestations and Presence of Borrelia burgdorferi sensu stricto, B. garinii,

B. afzelii, and B. Valaisiana in Humans. J Clin Microbiol. 1999 Dec; 37(12): 4086–

4092. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC85886/

19. Schwab, Jasmin; Claudia Hammerschmidt, Dania Richter, Christine Skerka, Franz-

Rainer Matuschka, Reinhard Wallich, Peter F. Zipfel, Peter Kraiczy. 2013. Borrelia

valaisiana Resist Complement-Mediated Killing Independently of the Recruitment of

Immune Regulators and Inactivation of Complement Components. PLoS One. 2013;

8(1): e53659. 10.1371/journal.pone.0053659. PMCID: PMC3539980.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539980/

20. Couper D, Margos G, Kurtenbach K, Turton S. 2010. Prevalence of Borrelia infection

in ticks from wildlife in south-west England. The Veterinary record 2010, 167:1012–4.

VIRAS response to: Who is the Focus?

And excluded groups placed at risk by the Draft Scope
30 1.1 Who is the focus?

49 Areas that will not be covered

51 Managing chronic fatigue syndrome. This is covered by the NICE 51 guideline: Chronic

fatigue syndrome/myalgic encephalomyelitis (or 52 encephalopathy) (CG53)

Abbreviations

AIDS, Acquired Immune Deficiency Syndrome

BIA, British Infection Association

CDC, Centres for Disease Control and Prevention, (USA)

CFS, Chronic Fatigue Syndrome

CRD, Centre for Reviews and Dissemination

DoH, Department of Health (UK)

FDA, Food and Drug Administration, (USA)

IDSA, Infectious Disease Society of America

LB, Lyme borreliosis

M.E., Myalgic Encephalomyelitis

HPA, Health Protection Agency

NATO, North Atlantic Treaty Organization

PCR, Polymerase Chain Reaction

PHE, Public Health England

WHO, World Health Organization

The following groups are at risk of being neglected by the NICE Guideline:

Infected in the past and presently ill due to:never investigated for LBnot investigated properly for LBmisdiagnosed with something other than LB

Since the Lyme disease spirochaete Borrelia burgdorferi was discovered in 1982 by Dr Willy Burgdorfer, multiple species of Lyme Borreliosis-causing spirochaetes have been found in Europe. In the decades following these discoveries, UK doctors have probably encountered many thousands of patients with symptoms highly suggestive of LB, just as doctors have in all the other countries of north-western Europe

Yet many of those doctors never considered Lyme borreliosis (LB) as a cause of their patient’s illness - let alone conducted a careful evaluation or ordered tests, because:

they had no experience of LB and little, if any, knowledge about the infection
UK reported incidence figures made LB appear rare (and therefore unlikely)
the doctor believed Lyme is only present in certain areas of the country
if they did order tests and the results were negative they wrongly believed this excluded LB (and may even have been told by the test laboratory staff that this was so)

In England and Wales, in the 15 years from 1997 to 2011 there were a total of 7,903 cases of LB reported at an average of 527 cases per annum giving an average annual incidence of ~0.93 per 100k population. (Public Health England. 2013.) This apparent rarity has meant that in past decades, many doctors were not alert to the risk of the disease, except perhaps for some of those practising in LB ‘hot-spots’. Yet significant risk to UK residents has been present and known to some, for decades

In 1993, Nuttall et al (1993) submitted data to NATO’s Second European Symposium on Lyme Borreliosis on the Ecology of Lyme borreliosis in the United Kingdom: showing that Ixodes ricinus (principal vector of LB in Europe) could be found throughout “Most of the UK” and that around 40% of unfed nymph and adult ticks “collected in Lyme disease foci” carried Borrelia burgdorferi, as shown by PCR

Thank you for your comment concerning chronic Lyme disease and post-Lyme disease syndrome. This clarification has been very helpful.