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Micro Exam 3 > Jackson: Zoonotic and Vector-Borne/ Bioterrorism > Flashcards

Jackson: Zoonotic and Vector-Borne/ Bioterrorism Flashcards

1
Q

Borrelia burdorgeri (Lyme Disease)

Virulence Factors:

A

Virulence Factors:

o Outer surface lipoprotein (Osp): contribute to arthritis and joint pain

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2
Q 
Borrelia burdorgeri (Lyme Disease)
Etiology:
A

Etiology:
o Vector of Transmission: Ixodes tick
• All life stages (larva, nymph, adult) harbor Borrelia, but ONLY nymph and adult transmit it
• Introduced into host by tick saliva and regurgitation
o Reservoirs: white-tailed deer, bear, white-footed mice
o No human to human spread

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3
Q 
Borrelia burdorgeri (Lyme Disease)
Erythema Chronicum Migrans:
A

Erythema Chronicum Migrans: red, bulls eye shaped lesions (clearing at site of tick bite)
• Diagnostic for tick bite
• Usually on thigh, groin, trunk or armpits

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4
Q 
Borrelia burdorgeri (Lyme Disease)
Three Stages

Early/First Stage:

A

o Three Stages:
• Early/First Stage:~1 week after tick bite (bacteria multiplying and disseminating)
➢ Fever, chills, fatigue, myalgia, athralgia

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5
Q 
Borrelia burdorgeri (Lyme Disease)
Three Stages

Secondary Stage (Acute):

A 
Secondary Stage (Acute): weeks to months after tick bite (bacteria have spread to CNS and joints)
➢	Acute arthritis, cardiac conduction defects, myopericarditis, neurological symptoms
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6
Q 
Borrelia burdorgeri (Lyme Disease)
Three Stages

Tertiary Stage (Chronic):

A 
Tertiary Stage (Chronic): months to years after tick bite (bacteria may or may not be present)
➢	Skin lesions, arthritis, neurological problems (autoimmune process due to Ag cross-reactivity)
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7
Q 
Borrelia burdorgeri (Lyme Disease)
Clinical ID:
A 
o	History of outdoor activity 
o	Bulls-eye lesion + flu-like symptoms 
o	Culture (Gram stain or immunostain) 
•	Blood, CSF or synovial fluid sampled 
•	Gram (-) spirochete
o	Borrelial Ag or Ab by ELISA or Western blot 
o	PCR
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8
Q 
Borrelia recurrentis (relapsing fever)
Virulence Factors:
A

Relapsing course of disease corresponds to variation in antigenic structure

Variable Major Protein (VMP)

  1. Antigenic determinants on cell surface that vary as selective pressure
  2. Cells recognized by host are killed
  3. VMP genes are activated by gene conversion
  4. Single clone can give rise to 20 distinct serotypes
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9
Q 
Borrelia recurrentis (relapsing fever)
Epidemic Louse-Borne Relapsing Fever

Vector:
Reservoir:
Transmission:

A
  • Vector: human louse Pediculus humanus
  • Reservoir: no animal reservoir
  • Transmission: person crushes louse and bacteria rubbed into bite wound; common in impoverished, overcrowded and poorly sanitized areas
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10
Q 
Borrelia recurrentis (relapsing fever)
Pathogenesis:
A

➢ Bacteria multiply locally and spread in blood stream
➢ Disease 10 days after bite (high fever and chills for 3-5 days, which remits in period cycles with decreasing severity)
➢ Other Sx include delirium, arthralgia and myalgia
➢ Rarely fatal

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11
Q 
Borrelia recurrentis (relapsing fever)
Endemic Tick-Borne Relapsing Fever

Vector:
Reservoir:
Pathogenesis:

A

Endemic Tick-Borne Relapsing Fever: more common US

  • Vector: soft tick (Ornithodorus)
  • Reservoir: rodents
  • Pathogenesis: bacteria remain in blood stream and DO NOT disseminate into tissues; symptoms similar to above
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12
Q 
Borrelia recurrentis (relapsing fever)
Clinical ID:
A

Peripheral blood smear (spirochetes seen with Giemsa stain)

Jarisch-Herxheimer Reaction (fever, chills, mualgia)

  • Complication seen with treating relapsing fever and other disease
  • Release of VMP from dying spirochetes triggers local inflammatory response
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13
Q

Leptospira spp. (Leptospirosis)

Infects domestic and wild animals:
Human contact with organism:

A

Infects domestic and wild animals: dogs are source of infection

Human contact with organism: urine contaminated water

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14
Q

Leptospira spp. (Leptospirosis)
Pathogenesis

Animals:
Humans:

A

Animals: chronic infection of the kidney

Humans: typically self-limiting, but can cause
• Hepatitis
• Bacteriuria (kidney)
• Scleral hemorrhage (in CSF and aqueous humor)

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15
Q

Leptospira spp. (Leptospirosis)

Clinical ID:

A

Spirochetes (visualized with dark field microscopy)

Can also measure serotype-specific Ab titers

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16
Q

Pasturella multocida
Etiology

Normal flora:
Infection in humans:

A

Etiology:
o Normal flora: of wild and domestic animals (nasopharynx)
o Infection in humans: usually associated with cat/dog bite or scratch
.

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17
Q

Pasturella multocida
Pathogenesis

Focal soft tissue infection:
Chronic respiratory infection:

A

Focal soft tissue infection: cellulitis within 1-2 days of bite/scratch

Chronic respiratory infection: in patients with chronic lung disease

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18
Q

Pasturella multocida

Clinical ID:

A

Routine cultures (BAP and CAP)
• Small, Gram (-) bacilli
• Oxidase (+)

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19
Q

Rickettsia ricketssii (Rocky Mountain Spotted Fever)

Virulence Factors: (2)

A

rOmpA: immunodominant surface exposed protein; mediates adhesion

Phsopholipase: mediates internalization of organism

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20
Q

Rickettsia ricketssii (Rocky Mountain Spotted Fever)

Vector:
Reservoirs:
Common in:

A

o Vector: Dermancentor ticks
o Reservoirs: dogs and other warm-blooded animals
o Common in Southeastern US: not so much in Rocky Mountains

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21
Q 
Rickettsia ricketssii (Rocky Mountain Spotted Fever)
Pathogenesis

Bacteria introduced at bite:
Infects:
Obligate intracellular anaerobes:

A

Bacteria introduced at bite: spread to bloodstream

Infects: vascular endothelium of lung, spleen, brain and skin

Obligate intracellular anaerobes: grow in cytoplasm and nucleus

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22
Q

Rickettsia ricketssii (Rocky Mountain Spotted Fever)

Symptoms develop ____ days after tick bite:

A

Symptoms develop 3-12 days after tick bite:
• Fever, headache, myalgia, nausea
• Petechiale or maculopapular rash on extremities (centripetal spread)
• Splenomegaly and neurological symptoms (from blood clots)
• Shock from multiple organ system failure)

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23
Q

Rickettsia ricketssii (Rocky Mountain Spotted Fever)

Mortality rate:

A

10%

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24
Q 
Rickettsia ricketssii (Rocky Mountain Spotted Fever)
Clinical ID:

G+/-?
Weil-felix Test:
Rickettsial Ag: (2)

A

Gram (-) coccobacilli (stains poorly)

Weil-felix Test (~ Quelling Reaction)

  1. Sera may agglutinate specific Proteus vulgaris strains
  2. Rickettsial antigens cross react with 3 Proteus O antigens
  3. Not very senseitive or specific, mostly of historic interest

Complement fixation with rickettsial Ag (4 fold rise in titer)

Indirect immunofluorescence with rickettsial Ag (IgG, IgM detected)

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25
``` Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Etiology ``` Reservoirs: Infection in Humans:
o Reservoirs: cats | o Infection in Humans: bacteria introduced by cat bites, scratches and licks
26
``` Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Pathogenesis ``` Basics:
* Causes chronic LN swelling in kids * Small papule at site of inoculation (persists for 2-3 weeks); lesion may supparate * Regional lymphadenopathy
27
Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Usually self limiting, EXCEPT in: immunocompromised
Usually self limiting, EXCEPT in immunocompromised
28
Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Bacillary angiomatosis (vascular infection):
Dissemination with sepsis or localized lesions of the skin (resemble Kaposi’s sarcoma)
29
Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Bacterial spread to major organs:
Hepatic and splenic peliosis (hemorrhagic lesions throughout parenchyma) Symptoms: o Target organ enlargement o Weight loss, nausea, fever o Elevated alkaline phosphatase levels (implies liver disease)
30
Bartonella henselae (Cat Scratch Disease, Bacillary Angiomatosis, Peliosis) Clinical ID:
Suggestive history and physical findings Aspirated pus from nodes: • Small, slightly curved Gram (-) rods • Fastidious Bacillary angiomatosis and peliosis diagnosed by histopathology and physical findings Serology + clinical findings leads to diagnosis
31
``` Ehrlichia chaffeensis (Ehrlichosis) Etiology ``` Vectors: Reservoirs:
Vectors: Ixodes scapularis ticks Reservoirs: small mammals
32
``` Ehrlichia chaffeensis (Ehrlichosis) Pathogenesis ``` Obligate intracellular pathogen: Symptoms: Severity:
Obligate intracellular pathogen: bacteria infect monocytes or granulocytes Symptoms: similar to RMSF (fevers, chills, headache, myalgia) but NO RASH Severity: can be fatal, but depends on severity of Sx
33
``` Ehrlichia chaffeensis (Ehrlichosis) Clinical ID: ```
o Rickettsia: G (-) coccobacillus o Indirect immunofluorescence for infected cells o Serological tests like ELISA (4 fold rise in titer)
34
Category A Diseases/Agents:
Category A Diseases/Agents: high-priority agents pose a risk to national security because they - Can be easily disseminated or transmitted from person to person - Result in high mortality rates and have the potential for major public health impact - Might cause public panic and social disruption (require special action for public healthy preparedness)
35
Category A Diseases/Agents Agents List: (6)
``` o Anthrax (Bacillus anthracis) o Botulism (Clostridium botulinum toxin) o Plague (Yersinia pestis) o Smallpox (variola major) o Tularemia (Francisella tularensis) o Viral hemorrhagic fevers - Filoviruses: Ebola, Marburg - Arenaviruses: Lassa, Machupo ```
36
Category B Diseases/Agents:
Category B Diseases/Agents: second highest priority - Moderately easy to disseminate - Result in moderate morbidity rates and low mortality rates - Require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance
37
Category B Diseases/Agents Agents list: (12)
``` o Brucellosis (Brucella species) o Epsilon toxin of Clostridium perfringens o Food safety threats • Salmonella spp. • EHEC • Shigella o Glanders (Burkholderia mallei) o Melioidosis (Bukholderia pseudomallei) o Psittacosis (Chlamydia psittaci) o Q fever (Coxiella burnetii) o Ricin toxin from Ricinus communis (castor beans) o Staphylococcal enterotoxin B o Typhus fever (Rickettsia prowazekii) o Viral encephalitis • Alphaviruses: VEE, EEE, WEE o Water safety threats: • Vibrio cholera • Cryptosporidium parvum ```
38
Category C Diseases/Agents:
Category C Diseases/Agents: third highest priority agents - Include emerging pathogens that could be engineered for mass dissemination in the future because of availability - Ease of production and dissemination - Potential for high morbidity and mortality rates and major health impact
39
Reasons for Concern: (3)
Plague: US and Soviet Union developed techniques to aerosolize plague bacillus; intentional dissemination via aerosol would result in pneumonic plague Anthrax: 2001 contamination of letters with anthrax spores Tularemia: one of the most infectious pathogenic bacteria we know o US military has stockpiles of weapons that would disseminate aerosols o Soviet Union engineered resistant strains
40
``` Bacillus anthracis (Anthrax) Virulence Factors: encoded on 2 separate plasmids ```
Virulence Factors: encoded on 2 separate plasmids o Polypeptide capsule made of D-glutamic acid: antiphagocytic o Anthrax Toxin: made of 3 elements
41
Anthrax Toxin:
Protective Antigen (PA): binding subunit; used for vaccine Edema Toxin: PA + edema factor (EF) - EF is an adenylate cyclase (increases cAMP) - Disrupts cell metabolism - Requires calmodulin as a co-factor Lethal Toxin: PA + lethal factor (LF) - LF is a metalloprotease that cleaves MAP kinases 1 and 2 - Short circuits major signal transduction pathway in monocytes
42
Bacillus anthracis (Anthrax) Primarily a disease of: Endemic areas: Ideal biological weapon due to:
Primarily a disease of herbivores: sheep, cattle etc. (humans rarely infected) Endemic areas: Asia, Africa, Middle East Ideal biological weapon: due to formation of endospores
43
``` Bacillus anthracis (Anthrax) Infection follows entry of endospores through injured skin/mucosa: ```
Spores in soil or contaminated animal products (hide, wool, bone) Spores highly resistant to disinfectants, heat, desiccation and UV radiation Remain viable for >50 years in the soil
44
``` Bacillus anthracis (Anthrax) Cutaneous Anthrax ```
Cutaneous Anthrax: spores contaminate scratch/abrasion and germinate in the tissue Toxins cause development of papule 12-36 hours later Development of painless ulcer with coal-black necrotic center Bacilli can spread to lymphatics, and untreated cases can spread to the blood (causing septicemia and death)
45
Bacillus anthracis (Anthrax) Inhalation Anthrax (Woolsorter’s Disease): Initial symptoms : RD:
Inhalation Anthrax (Woolsorter’s Disease): spores germinate in the lungs after inhalation Initial symptoms are non-specific (low grade fever, dry hacking cough, malaise) Respiratory distress with shock and sudden death - RD: due to massive pulmonary edema and mediastinal hemorrhage Antibiotic therapy may not even save patient
46
``` Bacillus anthracis (Anthrax) GI Anthrax: ```
GI Anthrax: ingestion of spores through contaminate meat (rare) - Abdominal pain, vomiting and bloody diarrhea
47
``` Bacillus anthracis (Anthrax) Clinical ID: ```
Collect fluid from local lesion, blood or sputum • Large Gram (+) bacilli • Non-motile • Non-hemolytic on BAP
48
``` Bacillus anthracis (Anthrax) Prevention: ```
Prevention: a vaccination is available for high risk groups
49
``` Yersinia pestis (The Plague) Virulence Factors: (3) ```
o Invasins o Type III Secretion: o Plasminogen Activator
50
``` Yersinia pestis (The Plague) Virulence Factors ``` Invasins:
Invasins: induce actin RAR in epithelial cells and facilitates uptake of bacteria into nonprofessional phagocytes (expressed at 20 degrees C)
51
``` Yersinia pestis (The Plague) Virulence Factors ``` Type III Secretion:
Type III Secretion: toxic products directly injected into mammalian cell cytoplasm - Yops (Yersinia outer membrane protein): effector Yops are kinase and phosphatase (disrupt actin and cytokine production → disruption of macrophage and PMN function) - Low calcium response (Lcr): released by type III secretion but NOT injected into cells (low Ca++ signal opens the pore formed by the Yops)
52
``` Yersinia pestis (The Plague) Virulence Factors ``` Plasminogen Activator:
Plasminogen Activator: activates plasminogen to dissolve fibrin clots and prevents chemotaxis of PMNs (may facilitate spread)
53
``` Yersinia pestis (The Plague) Etiology ``` Arthropod Vector: Animal Reservoir: Person to person transmission:
Arthropod Vector: rat flea regurgitates Yersinia upon blood meal Animal Reservoir: rats, ground squirrels, mice, antelope, domestic cats • Rats die in large number due to infection, precipitates movement of fleas from rat to human Person to person transmission: only with pneumonic plague
54
Yersinia pestis (The Plague) Bubonic Plague: Symptoms:
Bubonic Plague: most people infected by flea bite develop this Symptoms: appear 2-7 days after flea bite - Fever, lymphadenitis, vasculitis, bubonic purpura, gangrenous necrosis - Formation of buboes (large, grossly swollen LNs) - Gangrene of acral regions (peripheral parts of the body- “black death”)
55
Yersinia pestis (The Plague) Bubonic Plague Sepsis with no bubo (primary septicemic plague):
Sepsis with no bubo (primary septicemic plague): develops in small minority of patients - Hemorrhagic and necrotic lesions on all organs - Meningitis - Septic shock - High mortality rate (50-75%)
56
``` Yersinia pestis (The Plague) Pneumonic Plague: ```
Pneumonic Plague: occurs in a small number of patients with bubonic or septicemic plague Hematogenous spread Bronchopneumonia (person to person droplet spread) - Aerosol transmitted organisms are more virulent (adaptation to human host) Higher mortality rate than bubonic plague
57
Yersinia pestis (The Plague) Clinical ID: Prevention:
Clinical ID Specimen collection from blood, aspiration from buboes, sputum (pneumonic) - Gram (-) rod (safety pin appearance) - Immunofluorescence staining Prevention: vaccination available for high risk groups
58
``` Francisella tularensis (Tularemia or Rabbit Fever) Etiology ``` Reservoirs: Human Infection:
Reservoirs: carried by many species of wild rodents, rabbits, beavers and muskrats Human Infection: • Bitten by infected tick, deerfly or other insect • Handling infected animal carcasses • Eating or drinking contaminated food or water • Inhalation of the bacteria
59
``` Francisella tularensis (Tularemia or Rabbit Fever) Pathogenesis ``` Highly infectious: Different types of infection: (5)
Highly infectious: ID 10-50 bacteria Different types of infection: - Ulceroglandular (most common; cutaneous ulcer and lymphadenopathy) - Oculoglandular (conjunctivitis and lymphadenopathy) - Oropharyngeal - Pneumonic tularemia - Systemic tularemia (highest mortality- acute illness with septicemia)
60
``` Francisella tularensis (Tularemia or Rabbit Fever) Clinical ID: ```
Gram (-) pleiomorphic rod Can be grown in lab, but risk of lab-acquired infection is high
61
``` Brucella abortus (Brucellosis) Etiology ``` Causes ____ in animals In developed nations: Contracted by:
Causes spontaneous abortions in animals (cows) Rare disease in humans living in developed nations Contracted by: • Drinking unpasteurized milk • Direct contact with infected animal (skin abrasions, aerosol) • No person to person spread
62
``` Brucella abortus (Brucellosis) Pathogenesis: ```
o Relapsing fever o Enlarged LNs o Hepatitis
63
``` Brucella abortus (Brucellosis) Clinical ID: ```
Gram (-) coccobacilli (can be isolated from blood and urine) Rising titers to infection are diagnostic
64
Rickettsia prowazekii (Epidemic Typhus) Virulence Factors: Etiology Vectors: Reservoirs: Predisposing factors:
Virulence Factors: similar to R. rickettsii Etiology Vectors: human head and body lice (bites and defecates simultaneously, bacteria rubbed into wound) Reservoirs: flying squirrels Predisposing factors: poverty, overcrowding, poor sanitation
65
Rickettsia prowazekii (Epidemic Typhus) Course of Disease:
o Course of Disease: similar to RMSF (involves multiple organ systems and has higher mortality rate) o Brill Zinsser (BZ) Disease: recrudescence of old typhus infection (can survive in LN for 50 years with no symptoms; source of new typhus epidemic)
66
Rickettsia prowazekii (Epidemic Typhus) Clinical ID: Treatment:
Clinical ID: - Gram (-) coccobacillii - Complement fixation and immunofluorescence tests Treatment: control lice with insecticide
67
``` Coxiella burnetti (Q fever) Etiology: ```
Etiology: relative of Rickettsia but NOT transmitted by arthropod vector o Infection of livestock that is transmitted by aerosols (vets and handlers at risk)
68
``` Coxiella burnetti (Q fever) Q fever: ```
Q fever: respiratory infection accompanied by atypical pneumonia, headache and fever
69
``` Coxiella burnetti (Q fever) Clinical ID: ```
Gram (-) coccobaccili Indirect immunofluorescence assay 4 fold rise in complement fixing Ab titer

Micro Exam 3 (11 decks)

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