Borrelia (Lyme Disease)

Chapter 32
George Culver
Borrelia
Borrelia is a genus of zoonotic vector borne disease in the
spirochete phylum utilizing. Infects primarily mammals
using arthropods for vectors

Etiologic agent of Lyme disease and relapsing fever.

Lyme disease
B. burgdorferi (United States/Europe)

B. garinii (Europe/Asia)

B. afzelii (Europe/Asia)

Epidemic Relapsing fever

B. recurrentis (Epidemic Relapsing Fever)

Endemic Relapsing fever

Many species
https://en.wikipedia.org/wiki/Borrelia

Focus on B. burgdorferi, Responsible for Lyme in the United States

Structure
● Spiral shape
● .2-.5 by 8-30 um (comparatively large
for a spirochete)
● Membrane and Cell Wall
○ Outer membrane similar to
lipopolysaccharides, inner
membrane and peptidoglycan
layer in periplasmic space similar
to Gram-negative
○ Not classified as gram positive
nor negative due to poor staining
by gram stains
● Locomotion
○ Axial filaments in periplasmic https://www.semanticscholar.org/paper/The-unique-paradigm-of-spirochete-motility-and
-Charon-Cockburn/aabf9887f6ff4e6d3d9ecfc42958f2bc629ea7a2/figure/0

space called endoflagella. Propel

bacteria in corkscrew motion
Physiology

● Microaerophilic
● Complex nutritional needs
○ N-acetylglucosamine, Long chain saturated and
unsaturated fatty acid, Glucose, Amino acid
○ Difficult to culture with
● 18+ hour generation times.
● Differential gene expression in arthropod
vector and mammalian host
○ Outer surface protein A upregulated in midgut of
unfed ticks, down regulated when feeding, migrates
into salivary glands.
○ Outer surface protein C upregulated in mammals.
https://proteopedia.org/wiki/index.php/Sandbox1
 Lyme Disease
Infection progresses

● Early Localized Stage->Early Disseminated stage->Late Manifestation Stage

Early localised stage

● Erythema migrans (not pathognomonic)

● 3-30 days after infection lesion appears at tick bite
● 5cm-50cm area with red border and central clearing. “Bull’s-eye rash”. Fades
within weeks, new ones may form
● Rash often accompanied by: Malaise, fatigue, fever, chills, headache, myalgias,
lymphadenopathy.

Hematogenous Dissemination (Systemic signs of disease)

● Occurs within weeks in untreated patient

● Severe fatigue, Headache, fever, malaise, arthritis, arthralgia, myalgia, cardiac
dysfunction.

Late stage manifestations

● Develops if left untreated for many months to years

● Arthritis of many joints (60% of untreated individuals), acrodermatitis chronica
atrophicans (discoloration and swelling of skin), neurologic problems (insomnia,
numbness in hands/feet, facial palsy and can cause chronic encephalomyelitis among
other things.
https://commons.wikimedia.org/wiki/File:LymeYoungBoy14Oct2009.JPG
 Epidemiology
Distribution

● All 6 contents, more common in U.S, Europe and Asia

● Concentrated in Northeast, Mid-Atlantic and Upper Midwestern States

Transmission

● Transmitted from by hard ticks (Ixodes scapularis and I. Pacificus) from

mice (white-footed mouse) to humans
● 90% of infection from Ixodes nymphs which feed on only mice
● Larva takes blood mean from infected mouse becoming infected
https://www.cdc.gov/lyme/stats/maps.html
● Moults in late spring taking second blood meal, if on human then
prolonged feeding (more than 48 hours) can transmit the disease.
● Nymphs become adults in late summer and feed again open another
opportunity for infection
● Adult ticks feed on white tailed deer but can also infect humans at this
stage

Notes

● White tailed deer act as host for adult ticks and reservoir
● Ixodes nymphs are poppy seed sized
● Most infections occur from June-July

https://www.cdc.gov/ticks/life_cycle_and_hosts.html
Mechanism of pathogenesis and Clearance
Largely Unknown

What we do know

● Spirochetes found in, skin, heart, joints, peripheral and central nervous system and
symptoms may be caused by immune response to bacteria in tissue.
○ Possibly causes pathogen-induce autoimmune diseases due to molecular mimicry (1)
● Tick saliva
○ Tick saliva has anti-neutrophilic properties allowing initial proliferation and bull’s eye formation (2)
● Late disease
○ Spirochetes infrequently isolated in material from late in the disease
○ Unknown if live spirochetes cause late manifestation of disease
● Antigenic Shift
○ Carry many homologous OspC genes
○ Switch lipoprotein coat at rate of ~10-3 to 10-4 per generation
○ This behavior normally only observed for relapsing fever
○ May allow bacteria to persist months or years left untreated
● Clearance
○ Clearance mediated by months to years of IgG accumulation allowing for antibody mediated
complement clearance
 Laboratory Diagnosis
Serology Test

● Diagnostic levels of IgG or IgM antibodies against spirochetes

● Most common test for Lyme disease
● False positives occur due to cross reactive antibodies, low titers must be
analysed carefully (especially for people with syphilis)
● Immunofluorescence assay and Enzyme Immunoassay are the tests of
choice
○ Usually not sensitive during early acute stage (bull’s eye stage) due to
lack of antibodies
○ Westernblots used to confirm possible false positives https://www.researchgate.net/figure/Loosely-coiled-Borrelia-sp-in-a-thin-peripheral-bl
ood-smear-stained-with-Wright-Giemsa_fig2_224920163

Staining
● Isolation of Borrelia
● Stains well with Wright or Giemsa stain visible in light microscope
● Light microscopy blood smears used in relapsing fever but not Lyme due
to low count

Polymerase Chain reaction test

● Available, mostly used for research, relatively insensitive at around

65-75% when using skin biopsies
Treatment
Early Localised and Disseminated Lyme disease

● Orally administered amoxicillin, doxycycline or cefuroxime

● Early treatment greatly reduces chances of complications

Late term Lyme Infection

● Intravenous ceftriaxone, cefotaxime or penicillin

Chronic symptoms (post-Lyme disease syndrome)

● Treated symptomatically, treats the damage already caused

https://www.doctorfox.co.uk/chlamydia/doxycycline-antibiotics.html

by the bacteria.
Control
Reduce exposure to ticks
● Insecticide
● Insect repellent on clothing
● Tucking in clothing, lower skin exposure
● Change clothing after walking through grass or woods
Vaccination
● Vaccine against the OspA antigen of B. burgdorferi existed but
removed from market in 2002 due to lack of demand https://www.prevention.com/health/a
22095155/best-tick-repellents/
● Can’t eliminate borreliosis through vaccination.
Case Study: Persistent Lyme disease
Background: A 50 year old Caucasion woman from Virginia admitted to urgent care clinic with
shivering cold spells, fever, excessive thirst, 10/10 joint pain, and a large progressing rash on center
of the back. Patient also described a extreme headache of perceived tremendous helmet “as though
wearing a heavy helmet”. Three days prior to visit patient noted spider bite-like lesion on back (Day
one). Patient noted 39.3F fever and burning sensation of around bite mark and took ibuprofen and
Benadryl (Day 2). Patient completed the next day while feeling poorly (Day 3). Patent woke up with
symptoms leading to her seeking medical attention.

Examination: Initial exam showed 40.2oC temperature, 16x18cm bullseye rash on back. No
significant medical history related to case. Patient noted walk in the woods 3 weeks prior to visit but
did not find a tick.

Lab analysis: Blood work yielded normal white blood cell and platelet count and normal ranges of
hematocrit and hemoglobin. Serum chemistry yielded elevated glucose, slightly depressed
osmolarity, and borderline low alkaline phosphatase; Mostly unremarkable. Lyme serologic test
performed with ELISA taken that day yielded negative results for Borrelia (Day 1).

Second serological test demonstrated IgM but not IgG B. burgdorferi antibodies (Day 28). Lesion
biopsied yielding changes indicating lichenoid and spongiotic dermatitis while Steiner stain yielded
no spirochetes.

Treatment: 10 day doxycycline at 1000 mg a day prescribed. 4 days after treatment symptoms
improved enough to return to work. Day 9 body temperatures returned to normal with rash reduced https://doi.org/10.2147/imcrj.s51240
to 11x14cm. Doxycycline treatment extended at the same dose by 30 days
Persistent symptoms (Day 48)
Day 48: Patient admitted with neuralgia in lower extremities as well as tingling hands. Pain in legs described as “electric
currents running down legs”

Treatment: Second 30 day doxycycline treatment started at same dosage, 1000mg/day and gabapentin at 900 mg/day to
treat nerve pain. Patient was admitted to Lyme disease expert for continued management. At the time of article (several
years later) patient continues to report fatigue, intermittent arthralgia requiring occasion use of cane. Methylphenidate
taken to relieve symptoms of fatigue.

Notes:

● Erythema migrans was large but characteristic of Lyme. Necrosis at center as observed is uncommon but not
unheard of.
● Day 1 Symptoms severe but characteristic of stage I localized infection with viral-like symptoms.
● Day 48 symptoms characteristic of stage II, hematological spread which can affect the nerves (as seen in this
case), heart and skin.
● Lingering intermittent arthralgia characteristic of Stage III late LD which can manifest as, encephalopathy,
peripheral neuropathy, encephalomyelitis or arthritis as seen in this case.
● Negative day I elisia likely due to no activation of production of IgM and IgG antibodies.
● Doxycycline is normal drug of choice as it combats Anaplasma phagocytophilum, a common gram positive tick
borne co-infection
Sources
(General Data) Medical Microbiology 9th Edition, Patric R. Murray, Ken S. Rosenthal, Michael A. Pfaller

(Case Study) Palmieri, J., King, S., Santo, A., & Case, M. (2013). Lyme disease: case report of persistent Lyme disease from Pulaski

County, Virginia. International Medical Case Reports Journal, 99. https://doi.org/10.2147/imcrj.s51240

(1) Oldstone MB (October 1998). "Molecular mimicry and immune-mediated diseases". FASEB Journal. 12 (13): 1255–65.
doi:10.1096/fasebj.12.13.1255

(2) Fikrig E, Narasimhan S (April 2006). "Borrelia burgdorferi--traveling incognito?". Microbes and Infection. 8 (5): 1390–9.
doi:10.1016/j.micinf.2005.12.022
No reistance

If lyme has two membranes why is it not considered a gram negative or positive
bacteria?