Stakehold

state: “Preliminary estimates released by the Centres for Disease Control and Prevention

indicate that the number of Americans diagnosed with Lyme disease each year is around

300,000.

‘ “We know that routine surveillance only gives us part of the picture, and that the true

number of illnesses is much greater,” said Paul Mead, M.D., M.P.H, chief of epidemiology

and surveillance for CDC’s Lyme disease program. “This new preliminary estimate

confirms that Lyme disease is a tremendous public health problem in the United States,

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,

Ch. Schoerner, 1H. Hlobil,

Norris, J. Gensichen,

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.

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.

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.
			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)
VIRAS Vector- borne Infection, Research – Analysis - Strategy	Gener al	Gen eral	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) state: “Preliminary estimates released by the Centres for Disease Control and Prevention indicate that the number of Americans diagnosed with Lyme disease each year is around 300,000. ‘ “We know that routine surveillance only gives us part of the picture, and that the true number of illnesses is much greater,” said Paul Mead, M.D., M.P.H, chief of epidemiology	Thank you for your comment. This guideline will cover all people with Lyme disease regardless of their symptoms presentation or treatment history. The key areas were drafted in a way to ensure that those who clearly have Lyme, as well as those who may have Lyme but have never been investigated for Lyme receive the best possible assessment and diagnostic tests, and subsequently the best possible treatment.
			and surveillance for CDC’s Lyme disease program. “This new preliminary estimate confirms that Lyme disease is a tremendous public health problem in the United States,