Spirochetes. Gram ve, slender, cork-screw shaped

1

• Spirochetes
• Gram ve, slender, cork-screw shaped
• Periplasmic flagella
• Outer sheath (covering membrane ? mask the
  antigens
• Organisms
• 1. Treponema pallidum ? syphilis
• 2. T. pertune ? Yaws
• 3. T. carateum ? Pinta
• Syphilis
• Chronic STD
• Diagnosed by silver stains, Dark field, IF, but
  cant grow in cultures
• Spread ? sexual contact Transplacental
  (congenital)
• Trend ? incidence increasing
• Disease spectrum three stages

2

• Spirochetes
• Syphilis
• Primary syphilis
• Develops 3 weeks after contact
• Lesion chancre ? firm, nontender (painless),
  raised lesion on genitalia and anus, hard and
  indurated edges
• Spread by blood or lymphatics
• Resolves with or without Rx in 3-4 weeks
• Pathology ( seen in all stages of syphilis)
• Secondary syphilis
• Develop plasma cell and lymphocytic infiltrate
  with obliterative endarteritis 2-10 weeks after
  chancre
• Present as widespread skin rash ( palms, soles
  and moist areas ( where looks like condylomata
  caused by HPV) and generalized lymphadenopathy
• Lesions in mouth and vagina are most infectious
• plasma cell and lymphocytic infiltrate with
  obliterative endarteritis

3

• Spirochetes
• Syphilis
• Tertiary Syphilis
• Only in one third of un-Rx secondary syphilis pts
• Develops after 5 yrs
• Affects
• 1. CVS ? aortitis (dilation or aneurysm of aortic
  root ? AR)
• 2. CNS ? only in 30 pts., memingo vascular (
  Tabes dorsalis) or brain parenchyma ( General
  paralysis) CSF shows pleocytosis (? inflammatory
  cells), ? protein, ? sugar and antibodies ( CSF
  examination is the most specific test in
  Neurosyphilis)
• Benign tertiary syphilis Gummas (nodular
  lesions in response to delayed HSR like TB)
  affect bone, skin, mucous membrane, liver ( Hepar
  lobatum) white, rubbery have central
  Coagulative necrosis, with peripheral
  inflammatory cells ( plasma cells, macrophages)
  organisms are difficult to isolate

4

• Spirochetes
• Syphilis
• Congenital syphilis
• Transplacental infection
• Maternal infection ( primary or secondary) ?
  maternal blood testing for syphilis ? routine
  practice
• Lead to intrauterine or perinatal deaths in 25
  of cases
• Clinically
• Early (infantile) features ? lt2 yrs of life
  snuffles ( nasal discharge and congestion)
  blistering rash ( esp. hands, feet, mouth and
  anus) hepatomegaly with fibrosis and
  inflammatory cell infiltrate Gummas bones (
  osteochondritis and periostitis) lungs ? diffuse
  fibrosis in still born lungs are called
  pneumonia alba
• Late ( tardy) ? gt 2 yrs of age Triad of
  interstitial keratitis, Hutchisons teeth, VIII
  nerve deafness

5

• Spirochetes
• Syphilis
• Serologic tests
• Best for the diagnosis
• Can be
• Non treponemal? anti- cardilipin (VDRL) or
  specific reagin tests positive after 4-6 weeks
  of infections ve in secondary but ve in
  tertiary syphilis for screening and monitoring
  Rx ( cost-effective) false positive (acute
  infections, SLE, Drug addicts, pregnancy Leprosy
  etc.)
• Anti-treponemal? FTA or TPI positive in all
  stages and even after Rx (not for screening or
  follow-up) only in confirmation of diagnosis
• Pathogenesis
• No animal models and cant culture
• Obliterative endarteritis ? in all stages of
  disease
• Jarisch - Herxheimer reaction ? syndrome of High
  fever, rigors, hypotension and leucopenia while
  receiving Rx related to endotoxin release from
  the organisms ? cytokine storm also seen in Lyme
  disease

6
Primary syphilis
7
Gumma
8
Syphilis - stages
9

• Spirochetes
• Relapsing fever
• Vector borne (insect) recurrent fevers with
  spirochetemia
• Incubation period ? 1-2 weeks
• Clinically ? shaking chills, fever, headache,
  fatigue, DIC and MOF
• Relapses are due to ? temporary clearance
  followed by reappearance of antigenically
  different organisms
• Epidemic relapsing fever ? louse borne Borrelia
  recurrentis only in humans overcrowding
  mortality in one third of infected
• Endemic relapsing fever ? by many Borrelia
  (B.hermsii) vector is ornithodoras ticks
• Pathology ? Mild splenomegaly (louse borne) with
  congestion of red pulp moderate hepatomegaly
  secondary pulmonary bacterial infections

10

• Spirochetes
• Lyme Disease Place in Connecticut where there
  was an epidemic in 1970s
• Caused by Borrelia burgdorferi
• Transmitted from rodents by hard deer ticks
  (Ioxides) same can transmit Ehrlichia Babesia (
  hematologic parasites)
• Trend ? increasing
• Diagnosis serology is main
• Affect multiple organs
• Three stages
• Stage I multiplication of spirochetes at site of
  tick bite ( dermis)? Erythema chronicum Migrans
  fever and lymphadenopathy self limited
• Stage II early disseminate d stage blood spread
  ? fever, skin lesions (edema Lymphocytic
  infiltrate), migratory arthralgias and myalgias,
  lymphadenopathy, meningitis and Cranial Nerve
  damage
• Stage III after 2-3 yrs chronic arthritis with
  joint damage polyneuropathy and encephalitis
• Pathogenesis do not produce toxins tissue
  damage is mainly by immune response and
  inflammation arteritis (lupus like) with onion
  skin like lesions
• Bacterial lipoproteins TLR2(macrophages) ?
  Cytokines (Il-6, TNF, NO) ? ? (but not eliminate)
  bacterial load
• Adaptive immunity by CD4 and B cells but in
  effective because of Ag variation
• Plasmid encoded protein Vlse ? changes Ag
  structure every time
• Chronicity due to immune response to persistent
  bacteria

11
Stages in Lyme disease
12

• Anaerobic Bacteria
• Many normal flora
• Can cause diseases ( abscesses and peritonitis) ?
  Clostridium defficle associated antibiotic or
  pseudo membranous colitis
• Other environmental ones ? tetanus, botulism, gas
  gangrene
• Abscesses caused by anaerobes (mainly) and
  facultative aerobes ( mixed)
• Discolored foul smelling pus
• Anaerobes are derived from adjacent normal flora
  not produce toxins
• Head and neck Prevotella and Porphyromonas (
  Oropharyngeal flora)
• Lemierre syndrome ( pharyngeal abscess with
  Jugular vein thrombus) ? caused by Fusobacterium
  necrophorum
• Abdomen peptostreptococcus, clostridium (Gve)
  and Bacteroides fragilis,
• E. Coli (G-ve)
• Genital tract ( females) Prevotella (G-ve) and
  E. coli, Strep. agalactiae

13

• Anaerobic Bacteria
• Clostridial infections Gram ve spore forming
  bacilli
• Four types
• C. perfringens, C. septicum produce gas gangrene
  ( cellulitis and myonecrosis) in illegal
  abortions, food poisoning, small bowel ischemia
  and neutropenia
• Dead tissue is essential bacteria release
  collagenase and hyaluronidase
• ( degrade ECM proteins)? invasion
• Produces of toxins (a toxin most powerful)
  have multiple effects
• ( phospholipase C like lysis cell membranes
  sphingomylinase nerve sheath damage)
• Pathology of cellulitis foul smelling, thin,
  discolored exudate with extensive tissue damage
  disproportionate to of inflammatory cells (
  Neutrophils)
• Pathology of Gas gangrene life threatening
  exudative edema with enzymatic myonecrosis
  overlying skin shows blisters that rupture gas
  bubbles form due to bacterial fermentation
  affected muscle is blue-black, friable, semi
  fluid
• C. tetani cause tetanus due to puncture wounds
  or umbilical stump infections
• ( neonate) tetanospasmin ( neurotoxin) TT (
  tetanus toxoid) immunization
• Blocks the release of GABA ( inhibitory
  neurotransmitter) in the motor neurons? spastic
  paralysis
• Pathologic changes subtle and nonspecific

14
C. perfringens
15

• Anaerobic Bacteria
• Clostridial infections Gram ve spore forming
  bacilli
• Four types
• 3. C. botulinum in inadequately sterilized
  canned foods produces neurotoxin ? blocks
  release of Ach ? respiratory and skeletal muscle
  paralysis
• Toxin cleaves synaptobrevin protein ( fusion
  protein for transmitter containing vesicles with
  neuronal membrane ? inhibits release of Ach (
  stimulatory neurotransmitter) ? flaccid paralysis
• Botox ( botulinum toxin used in facial cosmetic
  surgeries)
• Pathologic changes subtle and nonspecific
• C. difficile pseudo- membranous colitis in
  antibiotic Rx pts.
• Toxin A (endotoxin) ? chemokine production
  leukocyte chemotaxis
• Toxin (cytotoxin) ? cytopathic effects
• Diagnosis by culture ( gas gangrene) or toxin
  assay (pseudo membranous colitis ) or both
  (botulism)

16

• Obligate Intracellular Bacteria
• Proliferate only in the host cells get the amino
  acids and the ATP from host cells ( using
  membrane pumps)
• Can survive extracelluarly
• Two groups of organisms
• Chlamydia cant synthesize ATP
• Rickettsiales can synthesize some ATP
• Chlamydia
• Gram ve
• exists in two forms
• Elementary bodies inactive, infectious
  particles, escape cytoplasmic Endosomes of host
  cells before phagocytosis
• Reticulate bodies active or replicate in host
  cells produce new elementary bodies
• Diseases
• 1. Trachoma ( childhood ocular infection)
  serotypes A, B, C)
• 2. Urogenital infections serotypes D to K
• 3. STD or Lymphogranuloma venereum (LGV)
  serotypes L1, L2, L3

17

• Obligate Intracellular Bacteria
• Chlamydia contd
• Diseases
• 1. Urogenital infections serotypes D to K
• MC STD in the world ( gt 2X the of Gonorrhea)
  previously called Non- Gonococcal Urethritis
  (NGU)
• Current CDC Rx protocol Rx Gonorrhea and
  Chlamydia as co infection
• Clinically resembles gonorrhea except
• Grams stain is negative
• Cant be cultured easily ( needs human cell
  lines)
• Urethritis in males may be asymptomatic
• Lymphogranuloma venereum (LGV) serotypes L1,
  L2, L3
• Chronic ulcerative disease
• Sporadic in USA and endemic in Asia, Africa,
  Caribbean and South America
• Starts as genital papule and lymphadenopathy
• Lymph nodes ? show granulomatous response with
  irregular necrosis and Neutrophilic infiltrate (
  stellate abscess) ? later fibrosis obstruction ?
  Lymphedema and strictures
• Rectal strictures more common in females

18

• Obligate Intracellular Bacteria
• Rickettsiales
• Vector borne infections
• Cause hemorrhagic fevers
• Do not produce toxins
• Immunity innate (NK cells) and later CMI (CTL)
  are critical
• Diagnosed clinically, immunostaining, serology
• Diseases
• Epidemic Typhus R. prowazekii
• Scrub Typhus Orienta Tsutsugamushi
• Rocky Mountain Spotted Fever (RMSF) R.
  rickettsii
• Erhlichiosis Ehrlichia or Anaplasma sps.
• Infects Neutrophils or Macrophages
• Tick borne
• Mulberry shaped cytoplasmic inclusions
• Presents with fever, headache, malaise later
  develop respiratory insufficiency, renal failure
  and shock

19
Erhlichiosis
20
Typhus
21
RMSF
22
Comparison of Rickettsial infections