Review
Special Issue: Zoonoses of people and pets in the USA
Lyme borreliosis in dogs and humans
in the USA
Susan E. Little1, Stephanie R. Heise1, Byron L. Blagburn2, Steven M. Callister3 and
Paul S. Mead4
1
Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA
2
College of Veterinary Medicine, Auburn University, Auburn, AL 86849, USA
3
Infectious Diseases Section, Department of Internal Medicine, Gundersen Lutheran Health System, La Crosse, WI 54601, USA
4
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA
Borrelia burgdorferi sensu stricto is the only established
etiologic agent of Lyme borreliosis in dogs and in
humans in North America. Lyme borreliosis differs in
dogs and humans in terms of clinical outcome following
infection, diagnostic approaches, prevention strategies
and treatment recommendations. Nonetheless, serolo-
gic evidence of exposure of dogs to B. burgdorferi
agrees with the geographical distribution of autochtho-
nous transmission of the agent of Lyme borreliosis, and
continued monitoring of exposure rates in dogs might
allow early recognition of geographic expansion of
endemic areas as well as identify hyperendemic areas
where both humans and dogs are at increased risk of
infection.
Humans, dogs and Borrelia burgdorferi
Humans and dogs are susceptible to illness from many of the
same tick-borne pathogens, including Borrelia burgdorferi
sensu stricto (hereafter referred to as B. burgdorferi), the
causative agent of Lyme borreliosis in the USA (Table 1).
Although they may occasionally infect ticks, domestic dogs,
like other wild carnivores such as skunks and raccoons, are
not important reservoir hosts for B. burgdorferi [1,2].
Rather, dogs and humans both become infected through
the bite of a vector tick infected as a larva or nymph while
feeding on a wildlife reservoir host (Figure 1). Because of
their lifestyle and contact with large numbers of ticks, dogs
are more likely to be exposed to B. burgdorferi, and canine
exposure may therefore serve as a marker for the risk for
human exposure. Several studies have successfully used
dogs to identify or confirm endemic foci of B. burgdorferi
and other tick-borne disease agents [3–9], although discrete
surveys, particularly during early invasion, may not be
sensitive enough to detect local activity [10].
The geographic distribution of tick-borne diseases var-
ies markedly within the USA, with Lyme disease and
anaplasmosis more common in the Northeast, upper Mid-
west and West Coast states, ehrlichiosis more common in
the South, and Rocky Mountain spotted fever (RMSF) most
common in the south-central and mid-Atlantic states [11–
13]. Expansions in tick populations may introduce disease
agents to new geographical areas [14,15]. This summary
Corresponding author: Little, S.E. (susan.little@okstate.edu)
1471-4922/$ – see front matter ß 2010 Published by Elsevier Ltd. doi:10.1016/j.pt.2010.01.006 Available online 6 March 2010
focuses on Lyme borreliosis, the tick-borne disease most
commonly recognized in humans and dogs in the USA.
Natural history – source of infection
Borrelia burgdorferi is transmitted to a variety of mam-
mals by certain Ixodes spp. ticks (Figure 1); I. scapularis
(commonly known as the deer tick) and I. pacificus (Wes-
tern black-legged tick) are the primary vectors in the
eastern and western USA, respectively. Both tick species
employ three-host life cycles, and nymphs, infected as
larvae during acquisition of bloodmeal from infected reser-
voir hosts, are the most important stage for B. burgdorferi
transmission to humans [16]. By contrast, dogs are con-
sidered to be infected primarily via adult ticks. Although
the white-footed mouse (Peromyscus leucopus) has long
been considered a primary reservoir host in the eastern
USA, recent data suggest that other small mammals, such
as shrews (Blarina brevicauda and Sorex cinereus) and
chipmunks (Tamias striatus), are also important sources of
infection [17].
Along the West Coast, the distribution of I. pacificus
correlates closely with cases of Lyme borreliosis in humans
and dogs [18], and there is a similarly close correlation with
the distribution of I. scapularis and Lyme borreliosis cases
in the upper midwestern and northeastern states. How-
ever, cases of Lyme borreliosis are rarely reported in the
Southeast, despite the presence of I. scapularis ticks
throughout the region. The timing of activity and behavior
of I. scapularis nymphs differs in the southern part of its
range, where this stage is much less active in the summer
months [16]. In addition, the immature stages of I. scapu-
laris in the Southeast more commonly feed on lizards,
which are less competent hosts of B. burgdorferi [19]. Thus,
although B. burgdorferi has been isolated from ticks and
rodents in the southern USA, transmission to humans or
dogs is significantly diminished by the feeding habits of the
immature I. scapularis [19,20]. In fact, autochthonous
human and canine infections with B. burgdorferi in states
south of Maryland and Virginia are rare [5,11].
Clinical Lyme borreliosis in humans and dogs
Lyme borreliosis, caused by infection with the spirochete
Borrelia burgdorferi, is the most commonly reported
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Review
Table 1. Key clinical features of Lyme borreliosis in dogs and humans.
Dogs
Clinical outcome b Majority (95%) of exposed dogs remain
following infection clinically normal
b If become ill, arthritis, fever, anorexia,
lymphadenopathy most common
b Glomerulonephritis may develop
Diagnostic approaches b Clinical signs consistent with Lyme
borreliosis and a history of exposure
in an area where disease is endemic
b Specific serologic test (C6)
b Quantitative C6-based assays available
to evaluate response to treatment
Prevention strategies b Routine vaccination in endemic areas
b Routine use of persistent acaricides
b Avoid tick-infested areas
b Habitat management around the home
(exclude wildlife, remove vegetative cover)
b Frequent tick checks and prompt removal
of attached ticks
Treatment Arthritis: doxycycline, 10 mg per kg q24h
recommendations PO for one month
Nephropathy: doxycycline, 10 mg per kg q24h
PO for one month or longer depending on severity
tick-borne disease in humans in North America [11,21] and
approximately 20,000 human cases of Lyme borreliosis are
reported in the USA each year [21]. The majority of cases
occur in the Northeast, upper Midwest and West Coast;
93% of cases are reported from 10 northeastern and mid-
western states [22]. The hallmark of human infection is
erythema migrans (Figure 2), a characteristic rash that
develops at the tick bite site in approximately 70–80% of
cases and is often accompanied by flu-like symptoms [22].
Left untreated, the spirochetes can then disseminate and
cause additional complications, such as arthritis, carditis
or neurologic disease [11]. By contrast, erythema migrans
is not known to occur in dogs. Rather, the illness often does
not become apparent until after the spirochetes have dis-
seminated and caused a combination of polyarthritis,
fever, anorexia and/or lymphadenopathy. In addition,
chronically infected dogs may develop a glomerulonephri-
tis syndrome referred to as ‘Lyme nephropathy’ [23]. The
pathogenesis of this syndrome remains controversial [24],
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Trends in Parasitology Vol.26 No.4
Humans
b Majority of exposed humans develop clinical signs
b Erythema migrans and flu-like illness most common
b Arthritis, carditis, neurologic disease may develop
b Clinical signs consistent with Lyme borreliosis and a
history of exposure in an area where disease is endemic
b Patients with EM and a history of exposure in an
area where disease is endemic may be diagnosed
without laboratory confirmation; laboratory testing
recommended for all other manifestations.
Recommended
b Serologic testing using whole cell antigen or C6
based assay followed by Western blotting of
specimens that test positive or indeterminate
b C6 assay preferred for patients with exposure
to European strains
Not Recommended
b Positive IgM test result alone for determining active
disease in patients with illness of greater than
1 month’s duration due to likelihood of a
false-positive result
b Urine antigen tests, immunofluorescent staining
for cell wall-deficient forms of B. burgdorferi,
lymphocyte transformation tests, PCR tests on
inappropriate specimens such as blood and urine,
Western blot assays interpreted using alternate criteria
b Avoid tick-infested areas
b Routine use of repellents
b Habitat management around the home (exclude
wildlife, remove vegetative cover)
b Frequent tick checks and prompt removal of
attached ticks
Erythema migrans (adults): doxycycline, 100 mg
q12h PO for 10–21d; amoxicillin, 500 mg q8h PO
for 14–21d; or cefuroxime axetil, 500 mg q12h
PO for 14–21d
Early neurologic Lyme disease (adults): ceftriaxone,
2g q 24h IV for 10–28d; or doxycycline 100–200 mg
PO q12h for 10–28d
Arthritis (adults): doxycycline, 100 mg q12h PO;
amoxicillin, 500 mg q8h PO; or cefuroxime axetil,
500 mg q12h PO for 28d
but dogs that develop nephropathy associated with B.
burgdorferi infection do not respond well to treatment,
and such cases are usually fatal [23].
Effective diagnostic strategies for Lyme borreliosis
The diagnostic approach for a tick-borne disease, as for any
infectious disease, is dependent on the biology of the
organism(s) in the host, the timing of clinical disease
relative to the infection and the immunological responses
during infection. For example, detecting organisms in
blood smears or by PCR of whole blood can reliably confirm
infection with other tick-borne disease agents such as
Ehrlichia spp. or Anaplasma spp., but these methods
are insensitive and inappropriate for diagnosing Lyme
borreliosis [25–27]. Spirochetes can be recovered by culture
from skin biopsies or other connective tissue; however,
detection can be difficult and is therefore not a requirement
for instituting antibiotic therapy [27]. Consequently, ser-
odiagnosis remains the mainstay of laboratory confir-
Review
Figure 1. Transmission cycle responsible for maintaining Borrelia burgdorferi in tick populations and allowing infection of humans and dogs. Nymphs are responsible for
transmitting the majority of infections to humans, whereas dogs are thought to be infected primarily via adult ticks.
Figure 2. Erythema migrans following tick bite. (Photo courtesy of S.E. Little.).
Trends in Parasitology Vol.26 No.4
mation for Lyme borreliosis [27–30]. Because serologic
tests are insensitive early in infections and late manifes-
tations are not pathognomonic, diagnosis of Lyme borre-
liosis relies on integration of clinical findings, sound
epidemiological knowledge of disease distribution and tra-
vel history, and correct use and interpretation of diagnostic
tests [11,23].
Most dogs infected with B. burgdorferi do not develop
clinical abnormalities associated with Lyme borreliosis, so
actively infected seropositive dogs must be discriminated
from dogs seropositive from past exposure by the presence
of appropriate clinical signs of illness [23]. However, dogs
that do develop clinical Lyme borreliosis usually do so
weeks or months after infection, at which time seroconver-
sion is likely and serologic testing is reliable [31]. By
contrast, humans usually develop objective clinical
abnormalities (such as erythema migrans) shortly after
infection and often in advance of seroconversion and, in
these instances, serologic testing can be unreliable.
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Review
Human patients with appropriate epidemiological
histories and early manifestations of Lyme disease (e.g.
erythema migrans) may be diagnosed correctly and treated
without the delay and expense of laboratory testing [11].
For humans with later stages of Lyme disease (e.g. arthri-
tis), serologic testing is sensitive and specific [32,33].
In human medicine, a two-tier approach is recommended
for serologic testing of patients with suspected Lyme disease
[28]. Samples are first tested using whole cell antigen to
detect IgM or IgG antibodies; samples that test positive or
indeterminate are retested by a Western blot in which at
least 2 of 3 (IgM) or 5 of 10 (IgG) characteristic bands are
identified [28]. When used appropriately for patients with
clinical symptoms and in areas where disease is endemic,
both sensitivity and positive predictive value of this
approach are high [33,34]. A well-established serological
response associated almost exclusively with B. burgdorferi
infection both in dogs and in humans, is the production of
antibodies that bind the VlsE protein [35]. Peptides (C6,
IR6) based on a distinct invariable region within VlsE form
the basis for highly specific serodiagnostic tests [32,35–37]
and there is evidence that this approach offers sufficient
sensitivity and specificity to eliminate the necessity of
additional serodiagnostic test procedures [30]. At present,
the C6-based assay is approved for use in humans as a first-
tier alternative to whole cell lysate-based assays.
In veterinary medicine, a simple, specific (100%; 95% CL
98–100%) patient-side C6 peptide-based assay has been in
widespread use since 2001, largely supplanting the
traditional two-tier approach for identifying specific anti-
bodies to B. burgdorferi [9,38]. Quantitation of this specific
response also is used for evaluating the effectiveness of
antibiotic treatment in dogs [37]. Similar tests (C6, IR6)
are used in diagnosing human illness [32,33,36] and may
be useful to evaluate response to treatment in the early
stages of Lyme disease in humans [39], but their ability to
discriminate active infection, especially during later stages
of the illness, remains unclear [40].
Treatment and prevention of Lyme borreliosis in
humans and dogs
Doxycycline is the recommended treatment for Lyme bor-
reliosis in dogs and for the most common forms of human
infection (Table 1); this antibiotic is also effective for treating
anaplasmosis, ehrlichiosis and RMSF [11,23,41,42].
Although doxycycline is not recommended for treating Lyme
disease in young children (<8 years of age), concerns regard-
ing tooth discoloration should not preclude its use during a
severe, potentially fatal illness (e.g. RMSF) [43]. Amoxicillin
and other beta-lactam antibiotics are also effective for treat-
ing B. burgdorferi, but penicillin derivatives lack efficacy
against the rickettsial pathogens, which may be occasional
co-infections during human and canine Lyme borreliosis.
Antibiotic treatment is most effective when instituted early
in the course of disease, and a single course of antibiotics is
considered adequate in most cases [11,23,42,43].
Some evidence suggests B. burgdorferi may persist in
some dogs following antibiotic treatment [44–47]. In one
study, viable spirochetes were recovered in culture from
dogs after either doxycyline or amoxicillin treatment [44],
although the presence of organisms was not associated
216
Trends in Parasitology Vol.26 No.4
with clinical disease in infected dogs [44] and some have
suggested the numbers or spriochetes may have been
waning [48]. Additional studies to determine the frequency
of treatment failures remain necessary. Experimental in-
fection work with mice has documented PCR evidence of B.
burgdorferi after antibiotic treatment [49,50], in I. scapu-
laris ticks fed on previously treated mice [50] and in SCID
mice on which those ticks fed [50]. However, spirochetes
were not isolated in culture from the mice or ticks, indi-
cating a reduction in either their number or viability
[48,50]. Re-infection with B. burgdorferi upon subsequent
exposure to infected ticks also occurs in both dogs and
humans [51,52].
A human B. burgdorferi vaccine is not currently avail-
able, but several vaccines are widely used to protect dogs
from B. burgdorferi. Estimates of efficacy range from 50%
to 85% [23], and the preventable fraction was >90% in one
field trial [53]. In addition, the vaccines do not induce
antibodies that are detected by C6-peptide based tests
[54]. However, whole-cell (but not subunit) vaccines induce
antibodies detectable on IFA or whole-cell ELISA that then
must be distinguished from those generated by natural
exposure [31]. In addition, vaccinated dogs may still
become infected because protection can be incomplete,
and the protective immune response wanes over time.
Limiting exposure to infected ticks remains a mainstay
for preventing Lyme borreliosis and other tick-borne dis-
eases. However, avoiding tick-infested areas might not be
feasible in many settings, particularly when the endemic
focus is immediately adjacent to the home. Therefore, the
Centers for Disease Control and Prevention (CDC) advises
frequent tick checks to remove crawling and attached ticks;
wearing light-colored clothing to facilitate tick detection;
appropriate use of repellents containing permethrin or
DEET; and landscape management to create ‘‘tick-safe
zones’’ for recreation (http://www.cdc.gov/ncidod/dvbid/
lyme/ld_prevent.htm). The Companion Animal Parasite
Council (CAPC) similarly recommends limiting exposure
of dogs to tick-infested areas, managing the habitat around
the home to exclude wildlife and reduce tick populations,
and routine use of acaricides on dogs (http://www.capcvet.
org). Routine acaricide use on dogs targets primarily the
adult stages of I. scapularis and may protect human health
by reducing the number of reproductively active adult ticks
in the environment immediately surrounding the home.
Although this protective effect has not yet been demon-
strated for Lyme borreliosis, routine use of insecticides and
acaricides on dogs has been shown to reduce the incidence
of visceral leishmaniasis in children in endemic areas [55]
as well as transmission of ehrlichiosis due to E. canis in
dogs [56,57].
Dogs as sentinels for Lyme borreliosis
Lyme borreliosis continues to impact significantly the
health of humans and dogs in the USA. The illness has
been historically confined to relatively limited geographi-
cal foci, and recent serological results from testing 982,336
dogs confirmed that canine exposure to B. burgdorferi
mimics the geographical distribution of reports of the ill-
ness in humans [5,9]. For example, in the northeastern
USA, 11.6% of dogs harbored specific antibodies to B.
Review
burgdorferi and prevalence was highest (>40%) in the
areas where human illness was most common [9]. How-
ever, endemic areas are likely to change [9,22] as habitat
modifications and climate changes affect distribution of
wildlife reservoirs and tick vectors [58]. Studies that
monitor the distribution of B. burgdorferi-infected ticks
by detecting exposure-specific antibody responses in dogs
may facilitate recognition of the movement of B. burgdor-
feri into previously non-endemic regions.
Conclusions
Ticks transmit a wide array of pathogens, harbor multiple
pathogens simultaneously and commonly transmit agents
that may produce long term infections without treatment, or
that may, upon re-exposure, establish new infections [50–
52,59–61]. Primary among these is transmission of B. burg-
dorferi to both humans and dogs by the bite of infected Ixodes
spp. ticks. Prevention strategies, diagnostic approaches,
treatment recommendations and clinical outcomes differ
between humans and dogs, and veterinarians, physicians
and pet owners should be aware of the significant differ-
ences. Integrated, collaborative research efforts by those in
public health and veterinary medicine could facilitate un-
derstanding of Lyme borreliosis and other tick-borne patho-
gens that cause disease in both dogs and humans.
Acknowledgements
This material developed out of a workshop held at the Centers for Disease
Control and Prevention (CDC) in Atlanta, Georgia in 2008 with invited
representatives from the Companion Animal Parasite Council (CAPC),
the CDC, the American Association of Veterinary Parasitologists and
others. Valuable input and support was received from Byron Blagburn,
Edward Breitschwerdt, Jennifer McQuiston, William Nicholson, Lonnie
King, Mary Bartlett and Sonya Hennessey. The authors also thank
Blaine Mathison for assistance in creating the life cycle figure, which was
developed by the authors and CDC’s Division of Parasitic Diseases DPDx
team.
The findings and conclusions in this report are those of the authors and do
not necessarily represent the official position of the Centers for Disease
Control and Prevention.
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