Lipsker D, Jaulhac B (eds): Lyme Borreliosis.

Curr Probl Dermatol. Basel, Karger, 2009, vol 37, pp 31–50

Epidemiology of Lyme Borreliosis

Zdenek Hubálek
Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Brno, Czech Republic

Abstract
Lyme borreliosis (LB) is the most frequent ixodid tick-borne human disease in the world, with an
estimated 85,500 patients annually (underlying data presented in this review: Europe 65,500, North
America 16,500, Asia 3,500, North Africa 10; approximate figures). This chapter summarizes the up-
to-date knowledge about facts and factors important in the epidemiology of LB all over the world.
Individual sections briefly describe geographic (latitudinal and altitudinal) distribution and inci-
dence rates of LB in individual countries; seasonal distribution of the disease; effects of patients’
age, sex, and profession; comparison of urban versus rural settings; weather-related effects on LB
incidence; risk factors for LB acquisition by humans; and risk assessment. This chapter finishes by
recommending a more thorough epidemiological surveillance for LB, including morbidity notifica-
tion in some additional countries where it has not yet been fully implemented.
Copyright © 2009 S. Karger AG, Basel

Introduction

Lyme borreliosis (LB), usually called Lyme disease (LD) in North America, is the most
abundant ixodid-borne disease of humans in the world, though it only occurs in the
northern hemisphere. It is in fact an old disease that was surprisingly only fully rec-
ognized at the end of the 20th century.
Several excellent reviews on LB epidemiology have been published previously
[1–7]. The purpose of this review is to summarize the up-to-date knowledge on, and dis-
cuss briefly all facts and factors important in, the epidemiology of LB over the world.

Geographic Distribution and Incidence Rate

LB occurs in North America (from the Mexican border in the south to the southern
Canadian provinces in the north), the whole of Europe, parts of North Africa
(Maghreb), and northern Asia (Russian Siberia and the Far East, Sakhalin, Japan,
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China, and Korea). In North America, only a few US states do not report LB or even
record it (Alaska, Arizona, Montana, Nebraska, New Mexico, and Wyoming). Occa-
sional reports of the occurrence of LB in the southern hemisphere (Central and South
America, sub-Saharan Africa, South Asia, Australia) have never been reliably con-
firmed. The geographic distribution of LB correlates closely with the range of the
principal vector, ticks of the Ixodes ricinus complex.

Incidence Rates

Incidence rates of LB in different countries are summarized in table 1. However, LB

is not a mandatorily notifiable disease in a number of European and North American
countries, e.g. Austria, Sweden, Switzerland (in the last decade), France, Belgium, The
Netherlands, Ireland, England and Wales, and Canada. Therefore, the incidence data
from these countries presented here are qualified estimates, based on several prospec-
tive epidemiological studies, usually limited to certain areas (very often those with a
high incidence of LB), and incidence rates of comparable neighboring countries. The
mean annual numbers of LB cases, as summarized from notified cases and qualified
estimates in countries without an obligatory notification system for LB, are 65,467 in
Europe; 3,450 in Asia; 16,340 in North America; and 7 in North Africa (Maghreb);
the annual world total is 85,264 LB cases. In a previous review, about 85,000 LB cases
were estimated in Europe only, with an additional 15,000–20,000 annual cases in the
USA [7]. Our estimates are more conservative.
Many experts admit that there is a significant underreporting of LB, and some of
them estimate that the real LB incidence rate may be 2–3 times higher than reported.
For instance, Campbell et al. [8] calculated an about 2.8-fold real incidence of LB in
Westchester county, N.Y., than that notified by the current passive reporting system.
A very similar figure was found in north-central Wisconsin, where only 34% of LB
cases were reported to the state, i.e. the real incidence was 2.9-fold higher [9]. Over-
reporting that follows overdiagnosis can also pose problems under certain circum-
stances (e.g. state of California in the first years of notification implementation). Nev-
ertheless, the reported figures that are presented here form a relatively good basis for
the comparison of LB incidence among countries, especially when the more recent
periods (1995–2006) are taken into consideration. If the coefficient of 3 is accepted
for underreporting, the mean total annual number of LB cases in the world might be
as many as 255,000.
Additional problems in LB notification are caused by different definitions of LB
cases, and diagnostic pitfalls with LB. A recent review [10] summarizes well most of
the problems associated with the clinical diagnosis of erythema migrans (EM) and
with various case definitions of LB in both North America and Europe [11, 12]. More-
over, the method used for the serological diagnosis of LB is not unimportant in that
different laboratories use various serological kits and tests, and the proportion of
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Table 1. Geographic distribution of mean annual incidence of LB (expressed mean annual LB cases per 100,000 of the
population)

Country Incidence Range Years Annual Remarks Reference number

(region) (per cases, n
100,000)

Europe (65,467)
Albania n.a. (5) no data about LB
Austria (130) (50–350) (4,500) not notifiable – 2, 3, 13
a rough estimate
Belarus n.a. (1,200) not notifiable 65
Belgium 12.58 8.2–16.3 1999–2006 1,297 Ducoffre, G.,
pers. commun., 2007
Bulgaria 5.44 1.9–13.0 1993–2005 433 Christova, I.,
pers. commun., 2007
Croatia 5.91 5.2–7.5 1993–2000 264 compulsory LB reporting 40
started in 1991
Czechland 31.73 14.0–61.2 1989–2006 3,263 LB reporting since 1990 108
Denmark 1.68 0.3–2.7 1994–2006 89 109
Estonia 31.01 14.3–43.8 1994–2006 424 notifiable 109 and Vasilenko, V.,
pers. commun., 2007
Finland 18.46 7.8–23.5 1999–2006 962 109
France 8.2 1999–2000 (4,900) 24
Germany (25) (18,000) not notifiable – except for 13, 49
6 eastern states
Eastern 6 states 26.05 17.8–36.5 2002–2006 4,440 notifiable in: Berlin, 47–49, 111
Brandenburg, Mecklenburg-
Vorpommern, Sachsen,
Sachsen-Anhalt, Thüringen
Great Britain
England 0.59 0.3–1.1 1997–2005 311 not notifiable; only 0.2% 110
and Wales seroprevalence in farmers
Scotland 1.72 1.6–1.9 2002–2005 87 notifiable 111
Greece n.a. (10) very low seroprevalence in 112
Navy recruits (ELISA 3.3%,
Western blot 0.3%)
Hungary 12.79 12.2–14.3 2001–2005 1,288 reportable 58
Iceland 0.56 0.0–1.1 1999–2003 2 seroprevalence 1–2%; 13, 109
B. garinii detected in
I. uriae in seabird colonies
Ireland 0.6 1995 25 no reliable data on incidence; 13 (estimate of Gray, J.)
not notifiable disease
Italy 0.02 0.001–0.5 2001–2005 11 notifiable since 1991 111
Latvia 21.64 11.7–30.6 1998–2006 507 notifiable 109
Lithuania 42.93 21.7–106.5 1995–2006 1,502 notifiable 109 (data of Asokliene, L.)
Luxembourg n.a. (60)
Moldova 0.73 0.7–0.8 2003–2005 31 Gheorghitsa, S.,
thesis, 2006
The Netherlands 2.01 1.4–2.7 2001–2005 327 not notifiable; 113
estimates of EM hospital
admissions
Norway 4.5 2.6–9.8 1992–2006 199 notifiable from 1989 to 1995 109, 111, 114
Poland 9.29 4.8–17.5 2000–2006 3,549 115
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Table 1 (continued)

Country Incidence Range Years Annual Remarks Reference number

(region) (per cases, n
100,000)

Portugal 0.48 0.2–0.8 1993–2004 49 serologic data on LB cases 116

0.04 0.01–0.15 1999–2004 4 notified cases; notifiable since 116
1999
Romania n.a. (1,500) LB occurs; seroprevalence:
4.3% (blood donors),
9.3% (forestry workers)
Russia 4.6 4.0–5.7 1999–2006 4,789 recorded since 1992 Korenberg, E.I., pers.
(European okrug) commun., 2007 (all okrug)
North-west 9.24 5.6–15.8 1999–2006 1,314
Central 3.39 2.1–4.7 1999–2006 1,263
Volga 6.8 5.8–8.5 1999–2006 2,192
Southern 0.09 0.04–0.17 1999–2006 20
Serbia and 2.44 1.4–3.3 1988–1994 239 50
Montenegro
Slovakia 12.12 6.3–18.4 1991–2006 650 51 and Bazovska, S., pers.
commun.
Slovenia 136.86 72–206 1991–2005 2,724 reported since 1988 20, 21, 111
Spain 9.8 (26) 7
Sweden 55–110 (8,000) http://www.socialstyrelsen.se Bennet, L., pers. commun.
Southern 69 26–160 1992 24% of the population, and 28
Sweden 11% of the area of Sweden
Northern very seroprevalence only 1–2%; infec- 13
Sweden low tion rate of I. ricinus only 0–5%
Switzerland 25.09 18.9–32.4 1988–1998 1,743 not reportable in the last 10 117
years
Turkey 0.01 1990–2002 1 <20 cases 1990–2002 118
(European part)
Ukraine n.a. (2,500) LB occurs Korenberg, E.I., pers.
commun.

North America (16,340)

USA1 5.78 3.2–8.4 1991–2005 15,840 22 (including states)
California 0.3 0.2–0.5 1993–2005 102
Connecticut 72.48 37.7–133.8 1991–2005 2,433
Delaware 24.4 7.8–76.6 1991–2005 189
Maryland 11.19 3.7–22.0 1991–2005 586
Massachusetts 11.98 2.5–36.5 1991–2005 847
Minnesota 8.81 3.1–20.1 1992–2005 429
New Hampshire 7.81 1.3–20.5 1991–2005 98
New Jersey 23.51 9.0–38.6 1991–2005 1,951
New York 24.12 15.5–29.2 1991–2005 4,502
(incl. NYC)
Pennsylvania 22.99 8.9–46.3 1992–2005 2,782
Rhode Island 47.49 15.6–79.7 1991–2004 459
Wisconsin 12.35 7.2–26.3 1991–2005 654
Canada low (500) not notifiable Ogden, N., pers. commun.
Ontario 0.25 0.2–0.4 1999–2004 29 Public Health Canada
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Table 1 (continued)

Country Incidence Range Years Annual Remarks Reference number

(region) (per cases, n
100,000)

Asia (3,450)
Russia (Asian part) 8.26 7.0–10.7 1999–2006 3,200 Korenberg, E.I.,
with the Urals pers. commun., 2007
(including okrug)
The Urals 9.81 7.3–13.9 1999–2006 1,226
Federal okrug
Siberian Federal 8.15 6.1–10.4 1999–2006 1,671
okrug
Far Eastern 4.33 3.1–5.8 1999–2006 303
Federal okrug
Sverdlovsk/ 14.7 1994 13
Jekaterinbg.
Novosibirsk area (10) 9–11.5 119
Tomsk region 28 1993–1994 29, 30
Turkey very <1 B. burgdorferi s.l. isolated from 118
(Asian part) low ixodid ticks
Kyrgyzstan low (20) B. burgdorferi s.l. isolated from Korenberg, E.I.,
ixodid ticks pers. commun., 1993
Kazakhstan very (10) LB likely to occur Korenberg, E.I.,
low pers. commun., 1994
Mongolia n.a. (5) no data about LB
China low (200) no incidence data available; 120, 121
B. garinii and B. afzelii isolates
from I. persulcatus and rodents
Taiwan <0.01 0.1 1 case of LB; also isolations of 122
B. burgdorferi s.l. from rodents
Korea very (5) no incidence data available; 120, 121
low B. garinii and B. afzelii isolated
from I. persulcatus and rodents
Japan <0.01 1987–1994 11 notifiable since 1999: 84 LB 120
cases since 1987 (mainly from
Hokkaido and Honshu);
many B. burgdorferi s.l. isolates
have been obtained from
patients and ixodid ticks

Africa 7
Morocco <0.01 <1 124
Algeria <0.01 <1 125
Tunisia 0.06 1992–1996 5 B. lusitaniae often isolated 126, 127
from local I. ricinus
Madeira Island <0.01 <1 2 cases in 1999–2004; 116, 123
seroprevalence in inhabitants
8.7%; at least 1.3% of nymphal
I. ricinus ticks infected with
B. burgdorferi s.l.

Incidence data (cases) in parentheses are qualified estimates, based on restricted prospective studies, extrapolation, incidence data
from neighboring countries, and population size. The figures without parentheses show the number of notified cases.
n.a. = No data (not available).
1 The listed states have the highest LB morbidity, except California.
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false-positive or false-negative serum samples might be relatively high in particular
circumstances [13, 14]. Probably the best serological assays at present are immunoas-
says (ELISA) for IgM and IgG antibodies, combined with immunoblotting.

Incidence Trends

In many countries, both in Europe and North America, no marked trends in the inci-
dence rate of LB have been recorded (just irregular fluctuations in the morbidity; for
references, see table 1), e.g. in Belgium, Switzerland, Czechland (syn. Czech Republic;
fig. 1), Slovakia, Hungary, Latvia, Estonia, Lithuania, Croatia, European and Asian Rus-
sia, and the US states of Connecticut, Rhode Island and New York, whereas other coun-
tries have reported a growing incidence of this disease in the last decade, e.g. The Neth-
erlands, Germany (eastern states), Norway, Finland, Denmark, England, Wales, Poland
and Bulgaria, and the US states of Pennsylvania, Wisconsin, Minnesota and Delaware.
However, some of these ‘increasing’ trends might be biased and caused, in fact, by an
improved notification system, greater awareness/vigilance, and better diagnostics for
LB over the last years in particular countries. For instance, it is of interest that in most
US states where LB is followed with great care for years (e.g. New England), no signifi-
cantly increasing trends of LB incidence have been recorded in the last decade.
LB reveals a distinctly focal pattern of distribution, even within small countries
and regions, that is determined by the heterogeneous spatial distribution of vector
ticks [15, 16]. The amount and composition of forest habitats (woodland) play a great
role, of course. Within the whole geographic range of LB, there are some hyperen-
demic high-risk areas (‘hot spots’), with annual incidences of 1100 LB cases per
100,000 of the population. Such districts have been reported in southern Sweden,
e.g. Blekinge County on the coastline along the Baltic Sea (mean incidence rate of 465
per 100,000 between 1997 and 2003, and a maximum of 664 in 2000 [17]), the Esto-
nian-owned island Saaremaa [385/100,000; Kutsar, K., pers. commun.], the Åland
islands of Finland (approx. 200/100,000 [18]), several Brandenburg counties in Ger-
many (Brieskow-Finkenheerd and Scharmützelsee, with 311 and 298 cases per
100,000, respectively, in 2003 [19]), the whole of Slovenia (1200 per 100,000 in some
parts of the country [20, 21]), certain parts of Austria, Connecticut (Old Lyme: up to
1,000 per 100,000), and Massachusetts (Nantucket County, with a morbidity rate be-
tween 449 and 1,247 per 100,000 from 1992 to 1999 [22]).

Influence of Latitude

LB occurs between approximately 35 and 60°N in Europe, and between 30 and 55°N
in North America. In countries at the southern limits of the LB range, its incidence
decreases rapidly along the north-to-south gradient. For instance in Italy, LB is quite
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 12 120
TBE
LB
TBE cases (per 100,000) 10 100

LB cases (per 100,000)

8 80

6 60

4 40

2 20

0 0
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
Year

Fig. 1. Incidence rates of LB and tick-borne encephalitis (TBE; transmitted by the same vector spe-
cies) in Czechland, 1992–2006 [108]. Pearson correlation between the incidence rates is highly sig-
nificant: r = 0.718 (p ! 0.01).

frequent in northern Italy, whereas it is much less common in central and southern
Italy [23]. The situation is similar in France [24], Spain [25], the Balkans (including
Bulgaria) [26, 27], and the southern states of the USA [22]. Conversely, at the northern
limits of its occurrence, the LB incidence decreases sharply with increasing latitude,
i.e. along the south-to-north gradient, e.g. in Scandinavia and European Russia [7, 13,
17, 28–30] or North America [12, 31]. This pattern closely reflects the distribution of
ixodid vectors of LB, which is determined by types of climate (mainly temperature
and humidity) permissive for the I. ricinus tick.

Influence of Altitude

A very low incidence of LB was observed at elevations 11,000 m above sea level (a.s.l.)
in Austria [32], although I. ricinus ticks infected with borreliae were recently detected
in Austrian mountains at 1,350 m a.s.l. [33]. In Czechland, I. ricinus has started to oc-
cur at higher altitudes, up to 1,100 m a.s.l., compared to elevations of up to only ap-
prox. 800 m a.s.l. two decades ago [34, 35]. It has nevertheless been demonstrated that
the prevalence rate of Borrelia burgdorferi s.l. in I. ricinus decreases with altitude, as
shown for example in Switzerland along an altitudinal gradient of 750–1,020 m a.s.l.
[36]. Already, Aeschlimann et al. [37] have reported individual ticks infected with
borreliae in Switzerland found at 1,250 m a.s.l. (Kiental), and their infection rate de-
creased with the elevation.
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Seasonal Distribution of LB

The annual distribution pattern of LB is strongly affected by the seasonal pattern of

host-seeking (questing) tick activity, lagged by the incubation period of LB which is
usually 1–4 weeks (but up to 2 months in a few cases; median is about 7–12 days) for
EM, 3–9 weeks (median 4–6) for early neuroborreliosis, 1.5–8 months (median 2) for
arthritis, 6–12 months for late neuroborreliosis, and several to many years for acro-
dermatitis chronica atrophicans (ACA) [13, 21, 24, 38, 39]. Therefore, LB as a disease
in all its forms occurs in all months of the year, although its incidence is (very) low in
late autumn, winter, and early spring – usually only chronic manifestations of LB (ar-
thritis, late neuroborreliosis, ACA) are reported in those periods. The peak of annual
LB incidence, the curve of which is usually unimodal, occurs from June to July in
Austria [32], Belgium [Ducoffre, G., pers. commun.], Bulgaria [27], Croatia [40],
Czechland [41, 42], France [43, 44], Germany [38, 45–49], Russia [39], Serbia [50], Slo-
vakia [51], Slovenia [21], southeastern Sweden [17], and the USA [5, 15, 22], indicating
that most infections are acquired during late May to late June. In northern countries
(Estonia, Sweden), the peak of LB incidence could include August [Kutsar, K., pers.
commun; 28], while in Alsace (France), May was reported as the peak [52]. In south-
ern Europe, sometimes a smaller secondary peak in the annual incidence rate of LB
occurs in autumn (October to November), when the local weather is warm and per-
missive for tick and human outdoor activity, e.g. in Slovenia [21].
In most countries, the timing of LB differs according to clinical manifestation. For
instance in Austria, the peak occurrence of EM is in July, whereas the peak for neu-
roborreliosis is in August and September [53]. Similarly, in southern Sweden, most of
the EM forms started in August, while the other clinical manifestations of LB peaked
in September [28]. This is caused by the different incubation periods for particular
clinical forms.
An additional factor affecting the seasonality of LB is human behavior and out-
door activity, i.e. the coincidence of maximum vector tick activity with summer-re-
lated leisure behavior of people [49]. For instance, vacation times overlapping with
enhanced exposure to vector ticks during hiking and berry/mushroom picking in
forests are usually June, July, and August in Europe [1].

Patient Characteristics

Lyme borreliosis could affect persons of all age categories, but the age distribution of
the disease is usually bimodal in most countries, with the first (lower) maximum oc-
curring in children 5–9 (14) years old, and the second (higher) maximum in adults
aged (45) 50–64 (69) years. A marked depression in LB morbidity appears among
young people between (15) 20 and 24 years of age. Such a pattern has been reported in
Belgium [Ducoffre, G., pers. commun.], Bulgaria [54], Croatia [40], Czechland [41, 42,
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55], England and Wales [56], Germany [38, 45–49], Hungary [57, 58], Serbia [50], Slo-
vakia [51], Slovenia [21], southeastern Sweden [17, 59], and the USA [5, 15, 22]. Interest-
ingly, a serological survey in Sweden also showed the bimodal pattern according to the
age groups: the antibodies against B. burgdorferi s.l. were most prevalent in children
and young persons below 20 years of age and in persons older than 50 years, while they
were much less frequent in persons aged 21–50 years, with an absolute minimum at
the 21- to 30-year-old group [60]. Explanation of the striking differences between age
groups could be related to the different outdoor activity and leisure-time behavior pat-
terns among these population strata [49]. However, some of these figures might be
biased in that most of them are not recalculated as specific incidence rates, i.e. cases
per number of inhabitants of a particular age category in the corresponding area.
Lymphocytoma manifestation occurs much more often or almost exclusively in
children under 16 years, whereas ACA is predominant in elderly persons [2, 11, 28,
38, 45, 57]. Also, neuroborreliosis and arthritis cases can be more frequent in children
than in adults [45]. Berglund et al. [28] reported the neuroborreliosis form of LB in
28% of children, but only 14% of adult patients in southern Sweden.
Bites of vector ticks vary in their localization on the human body between age
groups: in children they predominate on ears, head, and neck region (49% of bites vs.
2% in adults in Sweden, 23 vs. 1% in adults in Germany, 23 vs. 2% in adults in Bul-
garia), while in adults the predilection sites for ticks are the lower limbs: 62, 60, and
63.5% of bites in Sweden, Germany, and Bulgaria, respectively [28, 45, 54].

Sex

Results of gender-related analyses differ among countries. In the USA, males (51.9%)
slightly outnumbered females in 1992–1998, especially among children and adoles-
cents aged 5–19 years, but also in the category of adults aged 660 years [5, 15]. On
the other hand, a slight female preponderance (usual range of 54–60% females among
recorded LB patients) is reported in most European countries, e.g. Austria [53], Czech-
land [41, 61], Germany [45, 49], Slovakia [51], Slovenia [21], and Switzerland [37]. In
southeastern Sweden, among 3,443 EM cases reported in 1997–2003, 54.5% were fe-
males, and the predominance of females was especially marked in the age group 50–
74 years (60.1%) [59]. In Italy, females are infected more often than males [23], while
only 49.9% of the 1,175 LB patients in Hungary were female [57]. However, some of
these figures might be biased in that most of them are not recalculated as specific in-
cidence rates, i.e. per number of inhabitants of particular gender category in the cor-
responding area.
Females are affected more often than males by ACA, the late chronic cutaneous
manifestation of LB [2, 37, 38]. Reinfection with borreliae was reported 6 times more
frequently for females than for males in southern Sweden, and nearly all reinfected
women were older than 40 years and postmenopausal. Interestingly, Swedish females
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also attract more tick bites than males, though they spend approximately 30% less
time outdoors than men [59].
Bites of vector ticks vary in their localization on the human body between gender:
the predilection sites for ticks are the lower limbs and breast region in females, and
the lower limbs and genital region in males [28].

Occupation

Examples of population groups at risk are forestry workers, military field personnel,
farmers, deer handlers, gamekeepers, hunters, rangers, and outdoor workers in gen-
eral. For instance, LB seropositivity is high among forestry workers in most countries
tested: France 22% (while only 4% in normal population [62]), Austria 14–18% [2],
Bulgaria 18% [26] and Italy up to 27% [23]. Farmers also often have a higher seropos-
itivity rate, e.g. 15% in Bulgaria [26].
However, in most European countries, occupational exposure generally consti-
tutes only 2% of LB cases [63]; it is typically a recreation time disease, contracted dur-
ing holidays and leisure time exposure [24, 58, 63], including sport in forested areas.
In Switzerland, 8.1% of 558 orienteers seroconverted over 1 season, but only 0.8% of
them revealed clinical symptoms of LB – the ratio of apparent to inapparent infection
was therefore 1:9 [64].

Urban versus Rural Inhabitants

There is a low or no significant difference in LB incidence rates between urban and

rural populations [24], or the LB incidence among urban inhabitants is even higher,
e.g. in Finland where the mean morbidity (per 100,000 population) is 13 in Helsinki
but only 6.6 in rural areas [18], or in Russia where 84% of LB cases are among urban
residents [30, 65], and Bulgaria [54]. In addition, infected ticks also occur in urban
parks [66].

Weather-Related Effects on LB Incidence

In southeast Sweden and Scotland, LB incidence increased following mild winters (i.e.
number of days in preceding winter with mean temperature 10 ° C) and during warm
humid summers (i.e. the mean monthly summer temperatures combined with the
number of summer days with relative air humidity 186%), but higher mean monthly
precipitation (excess summer rainfall) had a depressing effect on LB morbidity [17, 67].
The authors have concluded that the main mechanism of these weather factors is either
increasing/decreasing precipitation, which also has an impact upon human outdoor
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activity (and subsequently the rate of human exposure to ticks) that is the leading
cause of LB morbidity. However, the tick activity should also be taken into consider-
ation. In 7 northeastern US states, the June moisture index (Palmer Hydrological
Drought Index) 2 years previously correlated well with the current LB incidence, most
probably by enhancing the nymphal I. scapularis survival during the more humid con-
ditions; further, a warmer winter, lagged 1.5 years, increased LB incidence, probably
due to the higher survival and activity of the white-footed mouse, the principal local
vertebrate amplifying host of borreliae [68]. Precipitation during May and June, not
temperature, stimulated LB incidence in the northeastern USA in the period 1992–
2002 [69]. Ashley and Meentemeyer [70] found that LB incidence is affected by meteo-
rological variables prevalent during April to June, and more by moisture (total soil
moisture surplus, total precipitation) than by mean air temperature, which could be
used for LB risk assessment. In general, summer temperature and rainfall affect tick
populations [71]. The effects of weather (and climate) on vector ticks are quite compli-
cated and simple solutions of the interrelationships are usually not the best ones.

Risk Factors for LB Acquisition by Humans and Risk Assessment

LB risk is clearly a product of 2 principal factors: the abundance (density) of infectious

vector ticks and the intensity of human exposure to the vector (degree of human-tick
contact).

Vector Tick Stage

The only competent vectors of pathogenic borreliae to humans are ticks of the I. rici-
nus complex: I. ricinus, I. persulcatus, I. scapularis, and I. pacificus. Most of the LB
patients are infected by nymphal rather than female Ixodes ticks, both in North
America and Europe [1, 63, 72–78]. Nymphs are more numerous in the field and, be-
cause of their smaller size, more difficult to be detected (at that moment and later) on
the human body than adult female ticks. In Connecticut 1989–1996, Westchester
county (New York state) 1991–1996 and South Moravia (Czechland) 1991–2001, 3 in-
dependent teams found that the local annual incidence of human LB correlated sig-
nificantly (R 2 = 58–69%) with the abundance of nymphal, but not female, vector ticks
[74, 75, 79].

Transmission Risk

The risk of developing LB symptoms after a vector tick bite is estimated to be 2–4%
[63], or sometimes even ^1% in Europe [4]. However, in a LB-endemic area of Poland,
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4.7% of 426 forestry workers bitten by a tick contracted clinical disease [80], and sim-
ilarly in Russia, LB transmission was reported in 4–5% persons with attached ticks
[30]. Nahimana et al. [78] followed 376 persons after a tick bite in Switzerland: EM
developed in 2.1% of the probands. In Germany, 2.6% of 730 persons with tick bites
developed LB [81]. In Sweden, 4.6% of persons with attached ticks seroconverted, but
not all of them revealed clinical symptoms of LB [82]. A seroconversion without LB
symptoms is quite common in Europe and results in a high seropositivity rate in the
European population [78]. In New England, the risk of LB after tick bites has been
reported to be 1.2% [83], 3.7% [84], and 3.2% [85].

Duration of Tick Attachment (Transmission Timing)

There is a difference between North America and Europe in the duration of tick at-
tachment required for transmission of borreliae into the human host. The US (Cen-
ters for Disease Control and Prevention) paradigm is that borreliae are only present
in the midgut of infected unfed (host-seeking) ticks, and during the blood feeding on
a host they migrate through the tick’s hemocele to salivary glands after 24–48 h, and
only then can the tick infect the host with saliva. In accordance with that, most North
American epidemiological studies state that transmission of borreliae to humans can
occur only 48 h after attachment [86]. This is obviously not correct for Europe, where
significant transmission of borreliae to the human host may occur within the first
24 h of attachment [63]. For instance, G. Stanek [pers. commun.] observed several
LB patients in Vienna who contracted LB following a tick attachment of no longer
than 8 h.
Importantly, generalized infection with borreliae (including the salivary glands)
has repeatedly been observed in some host-seeking unfed I. ricinus ticks, e.g. in Swit-
zerland [87–89]. These cases of systemic infection are probably most common with
the ticks containing large numbers of borreliae in their midguts – in some individ-
ual ticks thousands of borreliae have been observed. The proportion of unfed ticks
with 1100 borreliae were found to be 5.0% in 2,380 female and 1.7% in 3,546 nymph-
al I. ricinus examined in Czechland [90]; it is noteworthy that the prevalence rate of
the B. burgdorferi s.l. highly loaded nymphs (and females) closely matches the pro-
portion of tick bites giving rise to LB in humans (1–5%, see ‘Transmission Risk’).
Ticks with such a high spirochetal load can transfer them to the host much faster
than ticks with a low burden of borreliae [90, 91]. This difference between the Amer-
ican and European experiences could probably be explained by the quicker trans-
mission rate of B. afzelii and/or B. garinii than that of B. burgdorferi s.s. [92]. Kahl et
al. [93] found that half of experimental Mongolian gerbils (Meriones unguiculatus)
were already infected by spirochete-carrying I. ricinus nymphs 17 h after attach-
ment.
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Risk Assessment

Piesman et al. [72] proposed as a standard risk measure the number of infected ticks
per unit sampling effort (area, time). Ginsberg [94] formulated a simple transmission
risk index, the number of tick bites per person. Hubálek et al. [95] quantified the LB
risk exposure as the mean time necessary to encounter the first (heavily) infected tick,
measured by flagging. For risk assessment, Nicholson and Mather [31] suggested us-
ing the abundance of nymphal ticks and prevalence of borrelial infection in ticks, and
combine these with geographic information system analysis. An ecological risk index
[96] has been proposed to identify risk areas for LB transmission; it is composed of 5
components: habitat suitability, habitat amount, habitat accessibility, tick abundance,
and the tick infection rate (all classified on a scale of 1–5). However, this is not a very
useful predictor of LB incidence without taking into account the data on human be-
havior [97].
Risk ecosystems and habitats are deciduous or mixed forest ecosystems or wood-
lands matching the distribution of the principal vector (ticks of the I. ricinus com-
plex), along with city parks and urban gardens [45–48, 66], especially gardens within
200 m of forests [98]. In the Würzburg region in Germany, many cases of LB were
reported in the northwestern wooded area, but few cases in the southern, predomi-
nantly agricultural area [45]. Similarly in Brandenburg State, Germany, the majority
of LB cases were acquired in localities close to humid forests, while very low morbid-
ity has been reported in areas with extended agroecosystems [48]. Brandenburg,
steadily reporting about half of all LB cases from 6 eastern German states, is very rich
in forests and water habitats compared to the 5 other states [48].
There is a higher risk of contracting LB in the ecotones between forests and fields/
meadows, although higher densities of infected vector ticks are within forests; this is
an effect of frequent human presence along the edges of these habitats [99]. Also, for-
est fragmentation in suburban areas (Connecticut, USA) theoretically poses a greater
risk (higher entomological risk) due to an enhanced proportion of ecotones [100, 101].
However, in 1 study, the LB incidence was surprisingly lower in fragmented habitats,
and human behavior played a more significant role in the LB risk [102]. Prusinski et
al. [103] studied the effect of forest habitat structure on LB risk, and found that un-
derstory vegetation structure and coverage dictates vector density. On the other hand,
Nicholson and Mather [31] did not find plant communities as predictive in LB risk
assessment in a geographic information system-based analysis.
Ecological risk factors involve a number of variables. For instance, reforestation
usually causes an increased population not only of forest rodents, but also of deer, the
principal host of adult vector ticks. Growing deer populations (principal hosts of
adult vector ticks in woodland, but not competent hosts for borreliae) increase LB
morbidity [104]. In central Bohemia, Zeman and Januška [105] found that LB risk cor-
related with overall population density of game (red deer, roe deer, mouflon, wild
boar) regardless of mouse abundance. Nevertheless, in general, increased populations
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of competent hosts (forest rodents) usually stimulate the LB incidence. Increased
acorn production favors populations of forest rodents and deer, and results in an in-
crease in vector ticks [106].

Age and Sex

As shown previously, children and elderly people are at higher risk than middle-aged
persons. Bennet et al. [59] found that in southeast Sweden women 640 years old had a
48% higher risk of attracting tick bites than men of this age group, a 42% higher risk than
women younger than 40 years, and a 96% higher risk than men younger than 40 years.

Occupation

Outdoor employment and work (forestry workers, military personnel in the field,
farmers, gardeners, gamekeepers, hunters, rangers) are at risk.
Permanent residence in endemic areas with a high density of infectious ticks (e.g.
forested suburban localities in the US states of Connecticut, New Jersey, and New
York) is a serious risk factor for LB.

Risk Behavior

All activities that increase human contact with ticks present risks, especially: recre-
ational (leisure time) activities in forested areas, such as camping (including chil-
dren’s holiday camps), picnicking, walking and hiking, sitting on logs or on leaves,
jogging, orienteering, and berry/mushroom picking [107]; seasonal or occasional liv-
ing by urban residents in country cottages (‘dachas’) in endemic areas with a high
density of infectious ticks [26]; mowing and clearing of brush around the home in
forested areas and gardening, especially when the garden is within 200 m from a for-
est [98], even in urban gardens [16, 45]. In Scotland, the 2001 foot-and-mouth disease
outbreak led to countryside access restrictions, decreasing the visitor numbers during
summer months, which resulted in reductions in tick exposure and LB incidence [67].
Ownership of pet dogs and cats could also present a relative risk in cases where the
pets are frequently parasitized by ticks and the owner removes the ticks [98].

Epidemiological Surveillance

Epidemiological surveillance for LB is a paramount task for Europe, and this effort
should be coordinated by the European Centre for Disease Prevention and Control,
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44 Hubálek
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based in Sweden. It should include such things as improved awareness and recogni-
tion of the disease at national and continental levels, but first of all mandatory report-
ing of LB in all European countries where the disease occurs (and it occurs virtually
in all of them). Under certain circumstances, serosurveys among people, domestic
animals (dogs), and wild vertebrates might also bring useful results. Better surveil-
lance systems for LB should also be installed in some Asian, North African (Maghreb)
and North American (Canada) countries.

Acknowledgments

I am very much obliged to a number of experts who supplied the LB incidence data for particular
countries, or significantly assisted in obtaining these data (listed alphabetically): Loreta Asokliene
(Centre for Communicable Diseases Prevention and Control, Lithuania); Sylvia Bazovská (Ko-
menský University, Faculty of Medicine, Department of Epidemiology, Slovakia); Louise Bennet
(University Hospital of Malmö, Sweden); Iva Christova (National Centre of Infectious and Para-
sitic Diseases, National Reference Laboratory for LB and Leptospirosis, Sofia, Bulgaria); Gene-
viève Ducoffre (National Institute of Public Health, LB Reference Laboratory, Belgium); Lise Gern
(University of Neuchâtel, Switzerland); Johan Giesecke (ECDC Stockholm, Sweden); Jeremy Gray
(School of Biology and Environmental Science, University College, Dublin, Ireland); Agnetha
Hofhuis (RIVM – Epidemiology and Surveillance, Bilthoven, The Netherlands); Eduard I. Koren-
berg (Gamaleya Institute of Epidemiology and Microbiology, LB Reference Laboratory, Moscow,
Russia); Andras Lakos (Centre for Tick-Borne Diseases, Budapest, Hungary); Laurent Letrilliart
(University of Lyon, Department of General Practice, France); Catherine Linard (University of
Louvaine, Belgium); Elisabet Lindgren (CTM, Stockholm University, Sweden); Nicholas Ogden
(University of Montreal, Canada); Agostino Pugliese (University of Torino, Italy); and Veera Vasi-
lenko (National Institute of Health Development, Tallinn, Estonia).
This review was partially funded by the EU grant GOCE-2003-010284 EDEN; it is catalogued
by the EDEN Steering Committee as EDEN0063 (http://www.eden-fp6project.net). The contents
of this publication are the responsibility of the author and do not necessarily reflect the views of
the European Commission.

References
1 Jaenson TGT: The epidemiology of Lyme borrelio-
sis. Parasitol Today 1991;7:39–45.
2 Stanek G, Satz N, Strle F, Wilske B: Epidemiology of
Lyme borreliosis; in Weber K, Burgdorfer W (eds):
Aspects of Lyme Borreliosis. Berlin, Springer, 1993,
pp 358–370.
3 O’Connell S, Granström M, Gray JS, Stanek G: Epi-
demiology of European Lyme borreliosis. Zentralbl
Bakteriol 1998;287:229–240.
4 Gern L, Falco RC: Lyme disease. Rev Sci Tech 2000;
19:121–135.
5 Dennis DT, Hayes EB: Epidemiology of Lyme dis-
ease; in Gray J, Kahl O, Lane RS, Stanek G (eds):
Lyme Borreliosis: Biology, Epidemiology and Con-
trol. Wallingford, CABI, 2002, pp 251–280.
6 Piesman J, Gern L: Lyme borreliosis in Europe and
North America. Parasitology 2004;129(suppl):191–
220.
7 Lindgren E, Jaenson TGT: Lyme borreliosis in Eu-
rope: influences of climate and climate change, ep-
idemiology and adaptation measures; in Menne B,
Ebi KL (eds): Climate Change and Adaptation
Strategies for Human Health. Darmstadt, Stein-
kopff, 2006, pp 157–188.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong

Epidemiology 45
Downloaded by:
 8 Campbell GL, Fritz CL, Fish D, Nowakowski J,
Nadelman RB, Wormser GP: Estimation of the in-
cidence of Lyme disease. Am J Epidemiol 1998; 148:
1018–1026.
9 Naleway AL, Belongia EA, Kazmierczak JJ, Green-
lee RT, Davis JP: Lyme disease incidence in Wiscon-
sin: a comparison of state-reported rates and rates
from a population-based cohort. Am J Epidemiol
2002;155:1120–1127.
10 Tibbles CD, Edlow JA: Does this patient have ery-
thema migrans? JAMA 2007;297:2617–2627.
11 Stanek G, O’Connell S, Cimmino M, Aberer E,
Kristoferitsch W, Granström M, Guy E, Gray J: Eu-
ropean Union Concerted Action on Risk Assess-
ment in Lyme borreliosis: clinical case definitions
for Lyme borreliosis. Wien Klin Wochenschr 1996;
108:741–747.
12 Centers for Disease Control and Prevention: Case
definitions for infectious conditions under public
health surveillance. MMWR Recomm Rep 1997;46:
1–55.
13 World Health Organization: Report of WHO work-
shop on Lyme borreliosis diagnosis and surveil-
lance (who/cds/vph/95141-1). Warsaw, 20–22 June
1995, pp 1–220.
14 Hunfeld KP, Stanek G, Straube E, Hagedorn HJ,
Schörner C, Mühlschlegel F, Brade V: Quality of
Lyme disease serology. Wien Klin Wochenschr
2002;114:591–600.
15 Orloski KA, Hayes EB, Campbell GL, Dennis DT:
Surveillance for Lyme disease – United States,
1992–1998. MMWR CDC Surveill Summ 2000;
49:1–11.
16 Robert Koch-Institut: Risikofaktoren für Lyme-
Borreliose: Ergebnisse einer Studie in einem Bran-
denburger Landkreis. Epidemiol Bull 2001; 21: 147–
149.
17 Bennet L, Halling A, Berglund J: Increased inci-
dence of Lyme borreliosis in southern Sweden fol-
lowing mild winters and during warm, humid sum-
mers. Eur J Clin Microbiol Infect Dis 2006; 25:
426–432.
18 Junttila J, Peltomaa M, Soini H, Marjamäki M, Vil-
janen MK: Prevalence of Borrelia burgdorferi in Ix-
odes ricinus ticks in urban recreational areas of Hel-
sinki. J Clin Microbiol 1999; 37:1361–1365.
19 Robert Koch-Institut: Zur Lyme-Borreliose im
Land Brandenburg. Epidemiol Bull 2005; 20: 173–
178.
20 Strle F: Lyme borreliosis in Slovenia. Zentralbl Bak-
teriol 1999;289:643–652.
21 Strle F, Videčnik J, Zorman P, Cimperman J, Lotrič-
Furlan S, Maraspin V: Clinical and epidemiological
findings for patients with erythema migrans – com-
parison of cohorts from the years 1993 and 2000.
Wien Klin Wochenschr 2002;31:493–497.
46
22 Centers for Disease Control and Prevention: Re-
ports with statistics on Lyme disease cases. Morb
Mort Week Rep, continuously up to August 2007.
23 Ciceroni L, Ciarrocchi S: Lyme disease in Italy,
1983–1996. New Microbiol 1998; 21:407–418.
24 Letrilliart L, Ragon B, Hanslik T, Flahault A: Lyme
disease in France: a primary care-based study.
Epidemiol Infect 2005;133:935–942.
25 Estrada-Peña A, Oteo JA, Estrada-Peña R, Gortázar
C, Osácar JJ, Moreno JA, Castellá J: Borrelia burg-
dorferi sensu lato in ticks (Acari: Ixodidae) from
two different foci in Spain. Exp Appl Acarol 1995;
19:173–180.
26 Angelov L, Aeschlimann A, Korenberg E, Gern L,
Shchereva C, Marinova R, Kalinin M: Data on the
epidemiology of Lyme disease in Bulgaria (in Rus-
sian). Med Parazitol Parazit Bol 1990;4:13–14.
27 Angelov L, Arnaudov D, Rakadjieva T, Lipchev G,
Kostova E: Lyme borreliosis in Bulgaria. Report
WHO Workshop Lyme Borreliosis Diagn Surveill,
Warsaw, 20–22 June 1995, pp 41–52.
28 Berglund J, Eitrem R, Ornstein K, Lindberg A,
Ringner A, Elmrud H, Carlsson M, Runehagen A,
Svanborg C, Norrby R: An epidemiological study of
Lyme disease in southern Sweden. N Engl J Med
1995;333:1319–1324.
29 Korenberg EI: Ixodid tick-borne borrelioses
(ITBBs), infections of the Lyme borreliosis group,
in Russia. Report WHO Workshop Lyme Borrelio-
sis Diagn Surveill, Warsaw, 20–22 June 1995, pp
128–136.
30 Korenberg EI: Infections of the Lyme borreliosis
group – ixodid tick-borne borrelioses in Russia (in
Russian). Med Parazitol Parazit Bolez 1996; 3: 14–
18.
31 Nicholson MC, Mather TN: Methods for evaluating
Lyme disease risk using geographic information
systems and geospatial analysis. J Med Entomol
1996;33:711–720.
32 Stanek G, Flamm H, Groh V, Hirschl A, Kristofer-
itsch W, Neumann R, Schmutzhard E, Wewalka G:
Epidemiology of Borrelia infections in Austria.
Zentralbl Bakteriol Mikrobiol Hyg [A] 1986; 263:
442–449.
33 Stünzner D, Hubálek Z, Halouzka J, Wendelin I,
Sixl W, Marth E: Prevalence of Borrelia burgdorferi
sensu lato in the tick Ixodes ricinus in the Styrian
mountains of Austria. Wien Klin Wochenschr
2006;118:682–685.
34 Daniel M, Danielová V, Kříž B, Jirsa A, Nožička J:
Shift of the tick Ixodes ricinus and tick-borne
encephalitis to higher altitudes in Central Europe.
Eur J Clin Microbiol Infect Dis 2003; 22:327–328.
35 Zeman P, Beneš Č: A tick-borne encephalitis ceiling
in Central Europe has moved upwards during the
last 30 years: possible impact of global warming?
Int J Med Microbiol 2004; 293(suppl 37):48–54.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong
Hubálek
Downloaded by:
36 Burri C, Cadenas FM, Douet V, Moret J, Gern L:
Ixodes ricinus density and infection prevalence of
Borrelia burgdorferi sensu lato along a north-facing
altitudinal gradient in the Rhône Valley (Switzer-
land). Vector Borne Zoon Dis 2007;7:50–58.
37 Aeschlimann A, Chamot E, Gigon F, Jeanneret JP,
Kesseler D, Walther C: Borrelia burgdorferi in Swit-
zerland. Zentralbl Bakteriol Mikrobiol Hyg [A]
1986;263:450–458.
38 Wilske B, Steinhuber R, Bergmeister H, Fingerle V,
Schierz G, Preac-Mursic V, Vanek E, Lorbeer B:
Lyme borreliosis in South Germany. Epidemiologic
data on the incidence of cases and on the epidemiol-
ogy of ticks (Ixodes ricinus) carrying Borrelia burg-
dorferi (in German). Dtsch Med Wochenschr 1987;
112:1730–1736.
39 Korenberg EI, Kuznetsova RI, Kovalevskij JV, Vasi-
lenko ZE, Mebel BD: Basic epidemiological pat-
terns of Lyme borreliosis in the north-west of the
USSR (in Russian). Med Parazitol Parazit Bolez
1991;3:14–17.
40 Borčić B, Kaić B, Kralj V: Some epidemiological
data on TBE and Lyme borreliosis in Croatia.
Zentralbl Bakteriol 1999; 289:540–547.
41 Janovská D, Hálková B, Ranná M: Surveillance of
Lyme borreliosis in the Czech Republic. Abstracts
3rd Czech Days on Lyme Borreliosis, Prague, 27–29
Aug 1997.
42 Kříž B, Beneš Č: Lyme Borreliosis (in Czech).
Prague, National Institute of Public Health, 2007.
http://www.szu.cz/cem.
43 Dournon E, Villeminot S, Hubert B: Le maladie de
Lyme en France: enquête réalisée auprès d’un ré-
seau sentinelle de médecins généralistes. Bull Épi-
dém Hebd 1989;45:185–186.
44 Degeilh B, Pichot J, Gilot B, Allen S, Doche B,
Guiguen C: Dynamique annuelle des cas de pri-
moinfestation humaine de borreliose de Lyme
(erythème chronique migrant) en France et phenol-
ogie des populations de tiques vectrices (Ixodes ric-
inus Linné, 1758): essai de correlation. Acarologia
1996;37:7–17.
45 Huppertz HI, Böhme M, Standaert SM, Karch H,
Plotkin SA: Incidence of Lyme borreliosis in the
Würzburg region of Germany. Eur J Clin Microbiol
Infect Dis 1999;18:697–703.
46 Robert Koch-Institut: Zur Lyme-Borreliose in aus-
gewählten Bundesländern. Epidemiol Bull 2000;50:
395–398.
47 Robert Koch-Institut: Erkrankungen an Lyme-
Borreliose in den sechs östlichen Bundesländern in
den Jahren 2002 und 2003. Epidemiol Bull 2004;28:
219–222.
48 Robert Koch-Institut: Neuerkrankungen an Lyme-
Borreliose im Jahr 2004. Epidemiol Bull 2005; 32:
285–288.
Epidemiology
49 Mehnert WH, Krause G: Surveillance of Lyme bor-
reliosis in Germany, 2002 and 2003. Euro Surveill
2005; 10: 83–85. http://www.eurosurveillance.org/
ViewArticle.aspx?ArticleId=531.
50 Dmitrovic R: Lyme borreliosis in Yugoslavia 1987–
1994. Report WHO Workshop Lyme Borreliosis Di-
agn Surveill, Warsaw, 20–22 June 1995, pp 182–191.
51 Bazovska S, Machacova E, Spalekova M, Kontroso-
va S: Reported incidence of Lyme disease in Slova-
kia and antibodies to B. burgdorferi antigens de-
tected in healthy population. Bratisl Lek Listy 2005;
106:270–273.
52 Schmitt M, Encrenaz N, Chubilleau C, Verrier A:
Données épidémiologiques sur la maladie de Lyme
en Alsace, Limousin et Rhône-Alpes. Bull Épidém
Hebd 2006;27–28:202–203.
53 Stanek G, Kristoferitsch W, Hirschl A, Wewalka G:
Borrelia-Infektionen in Österreich 1984. Mitt Ös-
terr Ges Tropenmed Parasitol 1985; 7:55–62.
54 Christova I, Komitova R: Clinical and epidemiolog-
ical features of Lyme borreliosis in Bulgaria. Wien
Klin Wochenschr 2004;116:42–46.
55 Hulínská D, Janovská D, Bašta J: Lyme borrelio-
sis – epidemiological survey in the Czech Republic
in 1994. Report WHO Workshop Lyme Borreliosis
Diagn Surveill, Warsaw, 20–22 June 1995, pp 53–
75.
56 Smith R, O’Connell S, Palmer S: Lyme disease sur-
veillance in England and Wales, 1986–1998. Emerg
Infect Dis 2000;6:404–407.
57 Lakos A: Lyme borreliosis in Hungary. Report
WHO Workshop Lyme Borreliosis Diagn Surveill.
Warsaw, 20–22 June 1995, pp 84–102.
58 Epinfo (Epidemiológiai Informácios Hetilap):
Magyarország 2005. Évi Járványügyi Helyzete
2007;14:46.
59 Bennet L, Sternberg L, Berglund J: Effect of gender
on clinical and epidemiologic features of Lyme bor-
reliosis. Vector Borne Zoon Dis 2007;7:34–41.
60 Gustafson R, Svennungson B, Gardulf A, Stiern-
stedt G, Forsgren M: Prevalence of tick-borne en-
cephalitis and Lyme borreliosis in a defined Swed-
ish population. Scand J Infect Dis 1990; 22:
297–306.
61 Pazdiora P, Benešová J, Böhm K, Brejcha O, Kubá-
tová A, Machovská E, Mareš J, Morávková I,
Spáčilová M, Turková D, Vodrážková Z: Incidence
of Lyme borreliosis in the West Bohemian Region,
1988–1992 (in Czech). Epidemiol Mikrobiol Immu-
nol 1994; 43:71–74.
62 Doby JM, Couatarmanac’h A, Fages J, Chevrier S:
Les spirochétoses à tiques chez les professionnels de
la forêt. Arch Mal Profess 1989;50:751–757.
63 Gray J: Risk assessment in Lyme borreliosis. Wien
Klin Wochenschr 1999;111:990–993.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong
47
Downloaded by:
64 Fahrer H, van der Linden SM, Sauvain MJ, Gern L,
Zhioua E, Aeschlimann A: The prevalence and in-
cidence of clinical and asymptomatic Lyme borreli-
osis in a population at risk. J Infect Dis 1991; 163:
305–310.
65 Korenberg EI: Comparative ecology and epidemi-
ology of Lyme disease and tick-borne encephalitis
in the former Soviet Union. Parasitol Today 1994;
10:157–160.
66 Hubálek Z, Halouzka J, Juřicová Z: Prevalence of
borreliae in Ixodes ricinus ticks from urban parks.
Folia Parasitol 1993; 40:236.
67 Joss AWL, Mavin S, Ho-Yen DO: Increased inci-
dence of Lyme borreliosis following mild winters
and during warm, humid summers. Eur J Clin Mi-
crobiol Infect Dis 2007; 26:79.
68 Subak S: Effects of climate on variability in Lyme
disease incidence in the northeastern United States.
Am J Epidemiol 2003; 157:531–538.
69 McCabe GJ, Bunnell JE: Precipitation and the oc-
currence of Lyme disease in the northeastern Unit-
ed States. Vector Borne Zoon Dis 2004;4:143–148.
70 Ashley ST, Meentemeyer V: Climatic analysis of
Lyme disease in the United States. Clim Res 2004;
27:177–187.
71 Estrada-Peña A, Venzal JM: Changes in habitat
suitability for the tick Ixodes ricinus (Acari: Ixodi-
dae) in Europe (1900–1999). Ecohealth 2006;3:154–
162.
72 Piesman J, Mather TN, Dammin GJ, Telford SR,
Lastavica CC, Spielman A: Seasonal variation of
transmission risk of Lyme disease and human ba-
besiosis. Am J Epidemiol 1987; 126:1187–1189.
73 Hubálek Z, Halouzka J, Juřicová Z: A comparison
of the occurrence of borreliae in nymphal and adult
Ixodes ricinus ticks. Zentralbl Bakteriol 1991; 276:
133–137.
74 Hubálek Z, Halouzka J Juřicová Z: Longitudinal
surveillance of the tick Ixodes ricinus for borreliae.
Med Vet Entomol 2003; 17:46–51.
75 Hubálek Z, Halouzka J, Juřicová Z: Borreliae in Ixo-
des ricinus ticks feeding on humans. Med Vet Ento-
mol 2004; 18:228–231.
76 Falco RC, McKenna DF, Daniels TJ, Nadelman RB,
Nowakowski J, Fish D, Wormser GP: Temporal re-
lation between Ixodes scapularis abundance and
risk for Lyme disease associated with erythema mi-
grans. Am J Epidemiol 1999; 149:771–776.
77 Dorn W, Flügel C, Grübner I: Data on human-bit-
ing Ixodes ricinus ticks in a region of Thuringia
(Germany). Int J Med Microbiol 2002; 291(suppl
33):219.
78 Nahimana I, Gern L, Blanc DS, Praz G, Francioli P,
Péter O: Risk of Borrelia burgdorferi infection in
western Switzerland following a tick bite. Eur J Clin
Microbiol Infect Dis 2004; 23:603–608.
48
79 Stafford KC, Cartter ML, Magnarelli LA, Ertel SH,
Mshar PA: Temporal correlations between tick
abundance and prevalence of ticks infected with
Borrelia burgdorferi and increasing incidence of
Lyme disease. J Clin Microbiol 1998; 36: 1240–
1244.
80 Bialowas K, Jablonowski Z: Frequency of contact
with ticks and pathogenic effects of such contacts in
forestry workers of north-eastern Poland. Int J Med
Microbiol 2002;291(suppl 33):214.
81 Maiwald M, Oehme R, March O, Petney TN, Kim-
mig P, Naser K, Zappe HA, Hassler D, von Knebel
Doeberitz M: Transmission risk of Borrelia burg-
dorferi sensu lato from Ixodes ricinus ticks to hu-
mans in southwest Germany. Epidemiol Infect
1998;121:103–108.
82 Gustafson R, Svennungson B, Forsgren M, Gardulf
A, Granstrom M: Two-year survey of the incidence
of Lyme borreliosis and tick-borne encephalitis in a
high-risk population in Sweden. Eur J Clin Micro-
biol Infect Dis 1992; 11:894–900.
83 Shapiro ED, Gerber MA, Holabird NB, Berg AT,
Feder HM, Bell GL, Rys PN, Persing DH: A con-
trolled trial of antimicrobial prophylaxis for Lyme
disease after deer-tick bites. N Engl J Med 1992;327:
1769–1773.
84 Sood SK, Salzman MB, Johnson BJB, Happ CM,
Feig K, Carmody L, Rubin LG, Hilton E, Piesman J:
Duration of tick attachment as a predictor of the
risk of Lyme disease in an area in which Lyme dis-
ease is endemic. J Infect Dis 1997;175:996–999.
85 Nadelman RB, Nowakowski J, Fish D, Falco RC,
Freeman K, McKenna D, Welch P, Marcus R, Agüe-
ro-Rosenfeld ME, Dennis DT, Wormser GP: Pro-
phylaxis with single-dose doxycycline for the pre-
vention of Lyme disease after an Ixodes scapularis
tick bite. N Eng J Med 2001; 345:79–84.
86 Piesman J, Mather TN, Sinsky RJ, Spielman A: Du-
ration of tick attachment and Borrelia burgdorferi
transmission. J Clin Microbiol 1987; 25:557–558.
87 Lebet N, Gern L: Histological examination of Bor-
relia burgdorferi infection in unfed Ixodes ricinus
nymphs. Exp Appl Acarol 1994; 18:177–183.
88 Leuba-Garcia S, Kramer MD, Wallich R, Gern L:
Characterization of Borrelia burgdorferi isolated
from different organs of Ixodes ricinus ticks collect-
ed in nature. Zentralbl Bakteriol 1994; 280: 468–
475.
89 Zhu Z: Histological observations on Borrelia burg-
dorferi growth in naturally infected female Ixodes
ricinus. Acarologia 1998; 39:11–22.
90 Hubálek Z, Halouzka J, Juřicová Z: Investigation of
haematophagous arthropods for borreliae – sum-
marized data, 1988–1996. Folia Parasitol 1998; 45:
67–72.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong
Hubálek
Downloaded by:
 91 Korenberg EI, Gorban LY, Kovalevskii YV, Frizen
VI, Karavanov AS: Risk for human tick-borne en-
cephalitis, borrelioses, and double infection in the
pre-Ural region of Russia. Emerg Infect Dis 2001;
7:459–462.
92 Crippa M, Reis O, Gern L: Investigations on the
mode and dynamics of transmission and infectiv-
ity of Borrelia burgdorferi sensu stricto and B. af-
zelii in Ixodes ricinus ticks. Vector Borne Zoon Dis
2002;2:3–9.
93 Kahl O, Janetzki-Mittmann C, Gray JS, Jonas R,
Stein J, de Boer R: Risk of infection with Borrelia
burgdorferi sensu lato for a host in relation to the
duration of nymphal Ixodes ricinus feeding and
the method of tick removal. Zentralbl Bakteriol
1998;287:41–52.
94 Ginsberg HS: Transmission risk of Lyme disease
and implications for tick management. Am J Epi-
demiol 1993; 138:65–73.
95 Hubálek Z, Halouzka J, Juřicová Z: A simple meth-
od of transmission risk assessment in enzootic foci
of Lyme borreliosis. Eur J Epidemiol 1996; 12:331–
333.
96 Schulze TL, Taylor RC, Taylor GC, Bosler EM:
Lyme disease: a proposed ecological index to as-
sess areas of risk in the northeastern United States.
Am J Publ Health 1991;81:714–718.
97 Connally NP, Ginsbergh HS, Mather TN: Assess-
ing peridomestic entomological factors as predic-
tors for Lyme disease. J Vector Ecol 2006; 31: 364–
370.
98 Fitzner J, Ammon A, Baumann I, Talaska T, Schön-
berg A, Stöbel K, Fingerle V, Wilske B, Petersen L:
Risk factors in Lyme borreliosis: a German case-
control study. Int J Med Microbiol 2002; 291(suppl
33):220.
99 Horobik V, Keesing F, Ostfeld RS: Abundance
and Borrelia burgdorferi-infection prevalence of
nymphal Ixodes scapularis ticks along forest-field
edges. Ecohealth 2007;3:262–268.
100 Stafford KC, Magnarelli LA: Spatial and temporal
patterns of Ixodes scapularis (Acari: Ixodidae) in
southeastern Connecticut. J Med Entomol 1993;
30:762–771.
101 Fish D: Environmental risk and prevention of
Lyme disease. Am J Med 1995; 98(suppl 4A):2–9.
102 Brownstein JS, Skelly DK, Holford TR, Fish D:
Forest fragmentation predicts local scale hetero-
geneity of Lyme disease risk. Oecologia 2005;
146:469–475.
103 Prusinski MA, Chen H, Drobnack JM, Kogut SJ,
Means RG, Howard JJ, Oliver J, Lukacik G, Back-
enson PB, White DJ: Habitat structure associated
with Borrelia burgdorferi prevalence in small
mammals in New York State. Environ Entomol
2006;35:308–319.
Epidemiology
104 Steere AC: Lyme disease. N Eng J Med 1989; 321:
586–596.
105 Zeman P, Januška J: Epizootiologic background of
dissimilar distribution of human cases of Lyme
borreliosis and tick-borne encephalitis in a join
endemic area. Comp Immunol Microbiol Infect
Dis 1999;22:247–260.
106 Ostfeld RS: The ecology of Lyme disease risk. Am
Sci 1997;85: 338–346.
107 Lane RS, Steinlein DB, Mun J: Human behaviors
elevating exposure to Ixodes pacificus (Acari:
Ixodidae) nymphs and their associated bacterial
zoonotic agents in a hardwood forest. J Med Ento-
mol 2004; 41:239–248.
108 Epidat: Notification of Infectious Diseases in the
Czech Republic National Public Health Institute.
Prague, Centre of Epidemiology and Microbiolo-
gy, 2007. http://www.szu.cz/cema/hpcema.htm.
109 EpiNorth: Data on Lyme borreliosis. 2007. http://
www.epinorth.org.
110 Health Protection Agency: UK Data on Lyme bor-
reliosis. 2007. http://www.hpa.org.uk/infections.
111 Smith R, Takkinen J: Lyme borreliosis: Eu-
rope-wide coordinated surveillance and action
needed? Euro Surveill 2006; 11:E0606221.1. http://
www.eurosurveillance.org/ViewArticle.aspx?
ArticleId=2977.
112 Stamouli M, Totos G, Braun HB, Michel G, Giz-
aris V: Very low seroprevalence of Lyme borreliosis
in young Greek males. Eur J Epidemiol 2000; 16:
495–496.
113 Hofhuis A, van der Giessen JWB, Borgsteede
FHM, Wielinga PR, Notermans DW, van Pelt W:
Lyme borreliosis in the Netherlands: strong in-
crease in GP consultations and hospital admis-
sions in past 10 years. Euro Surveill 2006;
11:E060622.2. http://www.eurosurveillance.org/
ViewArticle.aspx?ArticleId=2978.
114 Hasseltvedt V: Cases of Lyme borreliosis notified
in Norway, 2000. Euro Surveill 2001; 5: 010809.2.
http://www.eurosurveillance.org/ViewArticle.
aspx?ArticleId=1706.
115 Epimeld: Infectious Diseases and Poisonings in
Poland. Warsaw, National Research Centre of
Public Health, 2007. http://www.pzh.gov.pl.
116 Lopes de Carvalho I, Nũncio MS: Laboratory diag-
nosis of Lyme borreliosis at the Portuguese Na-
tional Institute of Health (1990–2004). Euro Sur-
veill 2006;11:257–260.
117 Gern L: Lyme borreliosis in Switzerland. Report
WHO Workshop Lyme Borreliosis Diagn Surveill.
Warsaw, 20–22 June 1995, pp 152–156.
118 Güner ES, Hashimoto N, Takada N, Kaneda K,
Imai Y, Masuzawa T: First isolation and character-
ization of Borrelia burgdorferi sensu lato strains
from Ixodes ricinus ticks in Turkey. J Med Micro-
biol 2003; 52:807–813.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong
49
Downloaded by:
119 Romanova EV, Buchinskaya EA: Peculiarities of
clinical manifestations of tick-borne borrelioses
based on the data from 1st Novosibirsk City Infec-
tious Diseases Hospital (in Russian); in Matush-
enko AA (ed): Current Aspects of Diseases with
Natural Focality. Omsk, 2001, pp 123–124.
120 Miyamoto K, Masuzawa T: Ecology of Borrelia
burgdorferi sensu lato in Japan and East Asia; in
Gray J, Kahl O, Lane RS, Stanek G: Lyme Borrelio-
sis – Biology, Epidemiology and Control. Walling-
ford, CABI, 2002, pp 201–222.
121 Masuzawa T: Terrestrial distribution of the Lyme
borreliosis agent Borrelia burgdorferi sensu lato in
East Asia. Jap J Infect Dis 2004;57:229–235.
122 Shih CM, Wang JC, Chao LL, Wu TN: Lyme dis-
ease in Taiwan: first human patient with charac-
teristic erythema chronicum migrans skin lesion.
J Clin Microbiol 1998; 36:807–808.
Dr. Z. Hubálek
Medical Zoology Laboratory, Institute of Vertebrate Biology, Academy of Sciences
Klasterni 2
CZ–69142 Valtice (Czech Republic)
Tel. +420 519 352 961, Fax +420 519 352 387, E-Mail zhubalek@ivb.cz
50
123 Matuschka FR, Eiffert H, Ohlenbusch A, Richter
D, Schein E, Spielman A: Transmission of the
agent of Lyme disease on a subtropical island. Trop
Med Parasitol 1994;45:39–44.
124 Ouhabi H, Slassi I, El Aloui-Frais M: Paralysie fa-
ciale et maladie de Lyme. Arch Inst Pasteur Maroc
1994;9:51–55.
125 Rousselle C, Floret D, Cochat P, Reignier F, Wright
C: Encéphalite aige à Borrelia burgdorferi (maladie
de Lyme) chez un enfant algérien. Pédiatrie 1989;
44:265–269.
126 Aoun K, Kechrid A, Lagha N, Zarrouk A, Bouz-
ouaia N: La maladie de Lyme en Tunisie, résultats
d’une étude clinico-sérologique (1992–1996). Cah
Santé 1998;8:98–100.
127 Younsi H, Postic D, Baranton G, Bouattour A:
High prevalence of Borrelia lusitaniae in Ixodes
ricinus ticks in Tunisia. Eur J Epidem 2001; 17: 53–
56.
198.143.53.1 - 1/28/2016 10:33:04 AM
University of Hong Kong
Hubálek
Downloaded by: