Spirochetes

1
Spirochetes

• Borrelia spp
• Leptospira spp
• Treponema spp

2
(No Transcript)
3
(No Transcript)
4
Borrelia sp.

• Microaerophilic-to-anaerobic
• Loose, irregular coils
• many not cultivated in vitro
• Visualization
• silver staining
• darkfield microscopy
• Highly-adapted to arthropod transmission

5
Relapsing Fever

• Acute infection with febrile episodes
• septicemia, with fever, headache, muscle pain
• immune response lysis of bugs, shock due to
  endotoxin release
• patient returns to normal, usually 5-14 days
  between relapses
• Sporadic in US, distributed worldwide
• Antigenic variation
• single strain of B. hermsii
• progeny may represent more than 25 serotypes
• occurs without selective pressure of host immune
  response

6
Relapsing Fever

• Transmitted animal-to-animal, animal-to-human by
  ticks, human-to-human by lice
• Speciation
• louseborne disease B. recurrentis
• tickborne disease named after transmitting tick

7
Relapsing Fever

• Tickborne disease
• transmitted by soft ticks (genus Ornithodoros)
• O. turicatae, O. parkeri, O. hermsi in US, 15
  others worldwide
• US AZ, OK, CA, NM, CO, WA, TX, KS
• Louseborne disease
• body/headpubic lice (Pediculus humanus
  corporis/capitis/pubis)
• also bedbugs

8
Lyme Borreliosis

• Late 1970s, Old Lyme, CT
• Higher-than-expected incidence of childhood
  arthritis
• Pestered health officials, led to description of
  Lyme disease
• Caused by Borrelia burgdorferi
• Found in museum voucher specimens (mice, ticks)
  from early 20th century
• Most prevalent human tick-borne disease in the
  US, Europe, parts of Asia

9
Lyme Borreliosis

• Incubation period 7 - 14 days (range 3 - 30
  days)
• may be subclinical, manifest only nonspecific
  symptoms fever, headache, myalgia.
• First sign erythema migrans
• spirochetes multiply in skin, quickly enter
  circulation
• rash appears days-to-weeks after tick bite
• surround site of inoculation, expand in
  concentric rings
• disappear spontaneously after several weeks
• Second stage musculoskeletal signs (migratory
  joint, muscle pains), rare CNS signs, cardiac
  damage

10
Lyme Borreliosis

• Delayed humoral response
• circulating organisms killed by phagocytes,
  complement
• complement-independent antibody effects
• lack of LPS limits MAC formation without
  antibodies
• Some spirochetes not cleared from circulation
• localize inside host cells
• cross endothelium by disruption of tight
  junctions, transcytosis
• cell invasion key factor cardiac muscle, CNS
  damage
• Human transplacental transmission reported

11
Lyme Borreliosis

• Inflammation likely root cause of symptoms
• synovial cell colonization activates IL-8
  production
• potently chemotactic for PMN
• fibrin deposition, fluid accumulation
• Cellular response shifts to lymphocytes, plasma
  cells
• Chronic disease may be autoimmune-mediated
• anti-flagellar antibodies bind to cardiac, CNS
  antigens

12
Canine Lyme BorreliosisMost common domestic
animal host any breed, age, sex

• Sudden onset
• lethargy, inappetence, fever, swollen LN
• acute arthritis, increased synovial fluid
• Inflammation in joint space
• high synovial fluid cell counts (90 PMN), fibrin
• Swollen, edematous LN
• Also CNS infection
• cervical pain, depression, anorexia, seizures
• Fatal renal disease Lyme-specific immune
  complexes, complement deposition in glomeruli

13
Epidemiology

• Human encroachment into habitat of white-tailed
  deer
• Spread from deer, mice to humans by the bite of
  soft ticks
• adults, nymphs
• genus Ixodes, primarily I. scapularis (dammini)
• 2 year life cycle
• adult females produce 2000 eggs in spring
• hatch as uninfected larvae
• feeding on initial, infected hosts (mouse,
  lizards)
• emerge from dormancy following spring as infected
  nymphs

14

• quest for new hosts, mate after attaching to
  deer/other mammals
• female feeds to repletion, drops off, remains on
  ground until spring, cycle complete.
• Infection rate in nymphs 10 - 25, adult ticks
  60
• Important factor spirochete migration in tick
  during feeding
• migrates (24 - 48 h) from midgut to salivary
  glands
• short-term tick exposure gt no infection
• Intrauterine transmission in dogs
• Transplacental infections only direct
  human-to-human transmission
• Dogs not reservoirs for human infection

15
Prevention, Control, and Therapy

• Antimicrobial therapy
• successful for primary disease
• secondary or tertiary disease Rx often
  unsuccessful
• doxycycline, amoxicillin
• duration usually 4 weeks (slow multiplication, in
  vivo persistence)
• Dogs recover clinically in 24 - 48 h

16
Prevention, Control, and Therapy

• Immune response
• primary target outer surface proteins (Osps)
• humoral response develops slowly
• bactericidal antibodies peak after 3 - 5 weeks
• Serum antibody levels decline with Rx
• often rise over subsequent months
• suggest persistent infection
• Tick control important for prevention
• use of acaricides, repellents, daily grooming
• little positive from genocidal approach to deer
  populations

17
Leptospira interrogans

• 13 serogroups, gt200 serovars
• Disease in humans, domestic animals
• Zoonosis rodents, domestic animals
• Emerging infectious disease of humans?
• Most widespread zoonosis?

18
Epidemiology - Human Disease

• Temperate climates
• few serovars
• infection via direct contact infected farm
  animals (urine aerosols in milking parlors, milk
  of infected cows)
• Tropical climates
• many serovars (humans, domestic animals)
• many reservoirs
• exposure via environmental contamination
• Urban environment
• rodent-borne leptospirosis frequently misdiagnosed

19
Epidemiology

• Many serovars apparently host-adapted
• disease relatively mild, sporadic
• venereal transmission, lifelong colonization of
  genitourinary tract
• serovars hardjo (cattle), bratislava, tarassovi
  (swine)
• Others nonadapted
• catastrophic infections abortion storms, death
  of adults
• carrier state brief
• serovars pomona (swine, cattle), canicola (dogs)

20
Pathogenesis

• Enter through cuts, abrasions conjunctivae
• Evade local defenses, produce bacteremia shorter
  (host-adapted strains) or longer (nonadapted
  strains)
• Proliferate in liver, kidneys, spleen, meninges
• Antibodies, complement eliminate leptospires from
  blood stream, tissues other than brain, eye,
  kidneys
• multiply in proximal convoluted tubules
• excreted in urine by asymptomatic reservoir
  hosts few days to life

21
Pathogenesis

• Human disease
• nearly-subclinical, flu-like illness
• fulminant, fatal pulmonary hemorrhage hepatic,
  renal failure
• fatal human congenital infection
• Domestic animals
• fetal death, abortion

22
PathogenesisMechanisms

• Motility, attachment (fibronectin binding)
• Exotoxins sphingomyelinase
• Outer envelope antiphagocytic?
• Immune complexes associated with CNS inflammation
• Autoantibodies (anticardiolipin) in acute human
  illness
• Antileptospiral antibodies cross-react with
  equine ocular tissues
• involved in pathogenesis of recurrent uveitis
• retinal damage relates to presence of B
  lymphocytes in retina

23
Disease in Domestic Animals

• Cattle commonly serovars hardjo and pomona
• hardjo host-adapted
• sporadic abortions, infertility, mild clinical
  signs.
• female upper reproductive tract colonized,
  organism available for interaction with embryos
• localization in seminal vesicle infections
  transmitted at breeding
• pomona non-adapted
• more dramatic signs
• fever, icterus, hemoglobinuria
• abortion storms

24
Disease in Domestic Animals

• Swine serovars pomona and bratislava
• bratislava host-adapted
• clinical picture similar to hardjo in cattle
• subclinical disease, lifelong shedding
• pomona non-adapted
• infections similar to pomona in cattle
• abortion storms, fever, icterus, anemia,
  metritis, meningoencephalitis, death
• source may be wildlife (skunks, raccoons,
  opossums, deer)
• Horses
• bratislava adapted
• mild, sporadic infection of adults
• late-term abortions
• pomona, kennewicki nonadapted
• fever, icterus, abortion

25
Disease in Domestic Animals

• Dogs
• bratislava adapted mild disease, infertility,
  weak pups
• canicola non-adapted
• high fever, myalgia, bloody vomit
• vascular damage disseminated intravascular
  coagulation, melena, epistaxis, petechial
  hemorrhage
• renal localization, leptospiruria by 2 weeks PI
• acute nephritis progresses to chronic
  interstitial nephritis, renal failure

26
Treponema pallidumEndemic treponematoses affect
gt 2.5 million worldwide

• T. pallidum ss carateum (pinta), ss pertenue
  (yaws)
• ss pallidum 3stages of syphilis
• primary chancre, disappears spontaneously
• secondary penetrate mucus membranes, enter
  blood-stream, fever, rash
• tertiary invade heart, musculoskeletal system,
  CNS, relatively noninfectious

27
Syphilis

• Transplacental transmission during latency
• congenital syphilis1,000 US cases annually
• malformed teeth, long bones, cardiac lesions, CNS
  effects (learning disabilities, mental
  retardation)

28
Treponema pallidumVirulence Mechanisms

• Knowledge limited
• lack of in vitro cultivation
• maintained by serial passage in rabbit testicles
• no suitable in vivo model
• Lack of outer membrane proteins
• Protection from immune response by cloaking with
  host proteins
• Fibronectin binding
• treponemal antigen-fibronectin complex may gt
  antibodies vs fibronectin
• immune-mediated damage to cardiopulmonary,
  musculoskeletal, and central nervous systems in
  tertiary syphilis

29
Treponema brennaborensePapillomatous digital
dermatitis (hairy foot warts)

• 40 of US dairy herds
• Clinical signs
• episodic lameness, variable severity
• acute/chronic ulceration of skin on hoof
• cows walk on their toes
• Erosions of superficial epidermal layers, foul
  odor
• Lesions often surrounded by ridge of
  hyperkeratotic skin with hypertrophied hairs
  (hairy)
• Spirochetes deep in lesions