Lyme disease is a condition caused by the spirochete bacterium Borrelia burgdorferi which is spread to humans by certain types of tick bites
given the diverse symptomatology, it's ability to imitate many other conditions, and the apparent sometimes chronic nature of the symptoms, the diagnosis has become very controversial, and perhaps part of the confounding issue is that perhaps there are other similar conditions spread by other strains of related bacteria in different species of tick which are yet to be elucidated
B. burgdorferi sensu lato is made up of 21 closely related species, but only three clearly cause Lyme disease: B. burgdorferi sensu stricto (predominant in North America, but also present in Europe), B. afzelii, and B. garinii (both predominant in Eurasia)
genospecies of B. burgdorferi have been described and cause different patterns of disease:
B. burgdorferi sensu lato
B. burgdorferi sensu stricto - Nth America, Europe
B. andersonii - Nth America
B. bissettii - Nth America and possibly Europe
B. afzelii - Europe
B. garinii - Europe
B. spielmanii - Europe
B. lusitaniae - Europe
B. valaisiana - Europe and Continental Asia
B. sinica - Continental Asia
B. japonica - Japan
B. tanukii - Japan
B. turdae - Japan
ticks acquire Borrelia microbes from infected small mammals and occasionally birds, they then transmit these to deer, large mammals and humans
Vector geography
Blacklegged Tick (Ixodes scapularis)
mainly eastern half of USA
the north-east of USA is responsible for the far majority of reported cases in the USA
among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis
Western Blacklegged Tick (Ixodes pacificus)
west coast of USA
tend to feed predominantly on host species such as lizards that are resistant to Borrelia infection and this appears to diminish transmission of Lyme disease in the West of USA
sheep tick or castor bean tick (Ixodes ricinus)
the main vector in Europe
ticks along the eastern Baltic Sea, may also transmit tick-borne encephalitis
taiga tick (Ixodes persulcatus )
the main vector in China
lone star tick (Amblyomma americanu)
mainly eastern USA south of the Great Lakes
does NOT cause Lyme disease but Southern Tick-Associated Rash Illness (STARI) which has a rash indistinguishable from Lyme disease EM and may also be accompanied by fevers, headaches, fatigue, myalgias and arthralgias
causative agent not known
no evidence of Lyme disease being contracted in Australia
there may be similar diseases which are yet to be discovered from Australian ticks although spirochetes have been reported in Australian native animals which could theoretically act as a reservoir for an indigenous spirochete, so far no spirochetes have been detected in 12,000 tested Australian ticks
no ticks of the I. persulcatus complex, the principal vectors to humans in the northern hemisphere, occur in Australia
no significant difference was found in seroprevalence rates for B.burgdorferi infection in humans between high (rural residents) and low (urban residents) tick exposure groups, using an IgG ELISA. The overall seropositive rate was 2.2% which is thus most likely false positives due to cross-reactions.
Epidemiology
cases in USA appear to be increasing in line with re-forestation and the growth in wild deer numbers over the last century and the suburbanization of these reforested areas
affects all ages, but peak ages are children and middle aged adults in their forties
the far majority of cases in the USA occur in June or July, but they can occur all year round
an estimated 476,000 of diagnosed and treated cases of Lyme disease (LD) occur in the US each year1)
a 2024 survey of 70,000 adults in high risk areas in the Northeast, mid-Atlantic, and upper Midwest of USA suggested that 16% had tick bite within the prior 6 months and ~6% had a life time healthcare provider-diagnosed lyme disease2)
Clinical features
human infection from tick bites is greatest in late Spring, and in Summer
transmission of spirochaetes generally does not occur until after 24 hours attachment of the tick
incubation period
usually 1-3 weeks, but erythema migrans lesion may develop as early as 3 days after the bite
may be associated with an allergic reaction within hours of the bite, but this usually resolves within days
NB. in Australia, diagnosis can be confounded by a spectacular erythematous hypersensitivity reaction to the bite of I. holocyclus, the most common tick biting humans in New South Wales
stage 1
fever, fatigue, myalgias
headaches (in ~ 1/3rd)
meningism (< 10%)
arthralgias
lymphadenopathy
in 60-80% of cases, a characteristic skin lesion, erythema migrans (EM), appears 3-30 days after the bite (usually 7-14 days after the bite), usually at the site of inoculation
initial lesion is a red maculo-papular lesion greater than 5cm in diameter
rarely painful
expands and may reach more than 50cm in diameter, with central clearing and a well defined, circinate border creating a “bulls-eye” target like lesion
multiple lesions at various stages may be present
stage II
non-specific symptoms similar to secondary syphilis, weeks or months after the tick bite
carditis (~8% develop palpitations, a minority of these develop heart block)
chronic meningitis with CSF pleocytosis
mononeuritis (eg. cranial nerve palsies including facial nerve palsy / Bell's palsy which may be bilateral, or radiculopathy - dermatomal pain or numbness) (<20%)
conjunctivitis
arthralgia
myalgias
peripheral neuropathy
encephalopathy
stage III
symptoms occur months or years after the bite
erosive arthritis of large joints, particularly the knees (esp. if Nth American)
acrodermatitis chronica atrophicans (ACA) (esp. if European)
Diagnosis
two tiered serology
these tests individually can be unreliable due to cross-reactivity with other spirochaetes, bacteria, viruses and autommune diseases, but a two-tiered approach can give 95% specificity and sensitivity increases to around 90% or more if there is neurology or arthritis (sensitivity only ~40% in early EM phase and ~70% in convalescent EM phase)
IFAT (IFA) and ELISA (EIA) are used as initial screening tests
borderline or positive results should be confirmed by Western Blot (WB) which can detect protein bands specific for B. burgdorferi
if symptoms are < 1 month duration then do IgM and IgG WB, other wise just do IgG WB
if IFA or EIA negative, and symptoms cw Lyme disease and less than 1 month duration, then consider convalescent serology
PCR of punch biopsy of initial EM lesion
all current PCR tests have a high degree of false positives!
PCR synovial fluid
mod-high sensitivity if arthritis present
NB. PCR of CSF or blood has low sensitivity!
as with most tests, if the serology is done with a low pre-test probability, you may end up with a false positive rate of over 50%! UNDERSTAND YOUR PRE-TEST and POST-TEST probabilities!!
2% of the population have false positive IgG IFA/EIA serology!
patients can die from prolonged high dose iv antibiotics - most chronic symptoms do not respond to prolonged antibiotics - first do no harm!
Treatment
prophylactic post-exposure Rx of tick bite in USA
single dose doxycycline 200mg (4mg/kg for children aged 8 and over) IF:
attached tick is an engorged I. scapularis, and,
prophylaxis can be started within 72 h of tick removal time, and,
local rate of tick infection with B. burgdorferi is high (>20%)
Rx of Lyme disease
doxycycline 100 mg bd for 14–21 days, or,
amoxycillin 500mg tds
if neurologic features or stage III, consider IV ceftriaxone 2 g daily for 14-21 days
Prognosis
antibiotic therapy of early Lyme disease generally results in complete recovery
treatment of late stage Lyme disease is less successful and a chronic or relapsing course is common.
Historical background
1976: Steere et al. investigated a cluster of juvenile and adult arthritis cases in Connecticut
Soon recognized as late manifestation of multi-system disease associated with tick bite in US and Europe
1981: Burgdorfer et al. isolated spirochete from Ixodes ticks, then patients with erythema migrans
1982: first Australian cases of a syndrome consistent with Lyme disease were reported from the Hunter Valley region of New South Wales, but serologic testing was not definite and no positively confirmed cases acquired in Australia have been detected using the two-tiered serology method however, sensitivity of serological testing for Lyme disease sometimes depends on the strain of Borrelia used and could confound interpretation of results in Australia, where, as of 2012, no local spirochaete has been isolated for use as a reference antigen