Bacterial Zoonotics Flashcards

1
Q

Category A or Tier 1

Diseases/Agents

A

High-priority agents

  • Organisms that pose a risk to national security
  • Easily disseminated or transmitted from person to person
  • Result in high mortality rates
  • Potential for major public health impact
  • Might cause public panic and social disruption
  • Require special action for public health preparedness

Examples

  • Viruses:
    • Variola major (smallpox)
    • Viral Hemorrhagic Fevers
    • Filoviruses (Ebola, Marburg)
    • Arenaviruses (Lassa)
  • Bacteria:
    • Bacillus anthracis (anthrax)
    • Yersinia pestis (plague)
    • Francisella tularensis (tularemia)
  • Toxins:
    • Clostridium botulinum toxin (botulism)
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2
Q

Category B Diseases/Agents

A

Second highest priority agents

  • Moderately easy to disseminate
  • Result in moderate morbidity rates and low mortality rates
  • Require specific enhancements of CDC’s dx capacity and enhanced disease surveillance

Examples

  • Viruses:
    • Viral encephalitis
    • Alphaviruses ⇒ eastern equine encephalitis
    • Venezuelan equine encephalitis
    • Western equine encephalitis
  • Bacteria:
    • Brucellosis (Brucella species)
    • Burkholderia pseudomallei
    • Coxiella burnetii
    • Rickettsia prowazekii
    • Chlamydia psittaci
    • Food and water safety threats
      • Salmonella species
      • Escherichia coli O157:H7
      • Shigella
      • Vibrio cholerae
  • Toxins:
    • Epsilon toxin of Clostridium perfringens
    • Ricin toxin
    • Staphylococcal enterotoxin B
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3
Q

Category C Diseases/Agents

A

Third highest priority agents

  • 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
  • Emerging infectious diseases such as Nipah virus and hantavirus
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4
Q

Bacillus anthracis

Characteristics

A
  • Aerobic
  • Large, Non-Motile
  • Gram-⊕ Rods
  • Spore-formers
  • Animal products contaminated w/ anthrax spores include hides, bristles, hairs, wool and bone
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5
Q

Bacillus anthracis

Spores

A
  • Resistant to adverse chemical and physical environmental changes
  • Withstand dry heat and certain disinfectants
  • May persist in soil for years
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6
Q

Bacillus anthracis

Virulence Factors

A
  • Non-immunogenic, D-glutamic acid polypeptide capsule
    • Interferes w/ phagocytosis
  • Anthrax toxin ⇒ three components
    • Protective antigen (PA)
      • Mediates binding and entry into host cells
    • Edema factor
      • Calmodulin-dependent adenylate cyclase
      • Prominent edema @ site of infection
        • ⊗ Neutrophil function
        • ⊗ TNF and IL-6 production
    • Lethal factor
      • Zinc metalloprotease that ⊗ MAPKK ⇒ ⊗ cell signaling pathways
      • ⊕ MΦ production of TNF-α and IL-1β
      • Causes many signs and sx in anthrax
      • Acts on CNS ⇒ anoxia and respiratory failure
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7
Q

Bacillus anthracis

Pathogenesis

A
  • Infection usu. d/t entry of spores via skin and mucous membranes
  • Spores germinate @ site of infection
  • Vegetative form surrounded by proteinaceous fluid containing few leukocytes
  • Multiplies initially in MΦ
  • Subsequent extracellular replication and dissemination via lymphatics and blood ⇒ variety of tissues
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8
Q

Anthrax Disease

A
  • Caused by bacillus anthracis
  • Disease primarily of sheep and cattle
  • Man acquires disease accidentally
    • Usu. in an agricultural or industrial setting
  • In vivo:
    • Initial infection and replication occur w/in Mφ
    • Subsequent extracellular replication and dissemination
  • Three clinical manifestations of disease recognized
    • Depend on initial site of infection
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9
Q

Cutaneous Anthrax

A
  • Entry of the organism via breaks in the skin
  • Erythematous papule develops 12-36 hours later
  • Quickly progresses to formation of a pustule and then a necrotic ulcer (malignant pustule)
  • Infection may disseminate
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10
Q

Inhalation Anthrax

A

“Pulmonary Anthrax, Woolsorter’s Disease”

  • Acquired by inhalation of spores by handlers of raw wool, hides, or horse hair
    • May also be initiated by dissemination of dried B. Anthracis spores during bioterrorism attack
  • Spores germinate in lungs or tracheobronchial LNs
  • Sx include non-specific malaise, mild fever, and non-productive cough
  • Progressive respiratory distress and cyanosis follows
  • W/ massive edema of neck and chest
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11
Q

Gastrointestinal Anthrax

A

“Ingestion Anthrax”

  • Common in animals
  • Rare in humans
  • Infection in humans result in abdominal pain, N/V, and bloody diarrhea
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12
Q

Anthrax

Laboratory Diagnosis

A
  • Gram stain, culture and IF assays of fluid or pus from local lesions, blood and sputum
  • Cultured on normal blood agar ⇒ non-hemolytic gray colonies
  • Serological tests for Ab
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13
Q

Antrax

Treatment and Immunity

A
  • A variety of antibiotics are effective including:
    • Penicillin
    • Doxycycline
    • Ciprofloxin
  • Early treatment is important
  • Mechanisms of immunity unknown but likely rely on Ab-mediated mechs
  • Cutaneous anthrax ⇒ 95% of cases in the US
  • Cell-free vaccine available for humans w/ a high risk for exposure
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14
Q

Rickettsiae

Morphology

A
  • Small, rod-shaped bacteria (coccobacilli or pleomorphic, 0.3 - 0.7 μm)
  • Not readily stainable by Gram method
  • Can be stained w/ Giemsa
  • Peptidoglycan containing cell wall surrounding a cytoplasmic membrane ⇒ like a typical bacterial cell
  • Contain LPS and diaminopimelic acid (DAP) ⇒ like Gram-⊖ bacteria
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15
Q

Rickettsiae

Host Dependence

A
  • Obligate intracellular parasites
  • Depend on host cell for many functions:
    • Carbohydrate metabolism
    • Lipid synthesis
    • Nucleotide synthesis
    • Amino acid synthesis
    • Will utilize host ATP if it is available
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16
Q

Rickettsiae

Virulence

A
  • Multiply in endothelial cells of blood vessels
  • Causes endothelial proliferation and perivascular infiltrationleakage and thrombosis
  • Vasculitis particularly evident in small blood vessels in major organ systems
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17
Q

Rickettsiae

Immunity

A
  • Opsonizing Ab and phagocytosis play a role in clearing Rickettsiae from the bloodstream
  • Organisms are intracellular ⇒ cell-mediated immunity may also contribute
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18
Q

Rickettsiae

Culture

A
  • Can be cultivated in embryonated eggs and tissue culture cells
  • Fails to grow on artificial media
  • May be d/t defect in the membrane of Rickettsiae
    • Does not permit retention of small molecules once removed from living cells
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19
Q

Rickettsiae

Laboratory Diagnosis

A
  • Isolation of rickettsial agents in tissue culture not used in clinical settings
  • Use of dx PCR-based assays is ↑
  • Laboratory dx relies heavily on serological tests:
    • Complement fixation
    • Indirect immunofluorescence
    • Latex agglutination
  • Weil-Felix reaction
    • Cross-reactivity and agglutination of certain strains of Proteus
    • Not used as dx tool d/t poor sensitivity and specificity
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20
Q

Rickettsiae

Treatment

A
  • Doxycycline, tetracycline, or chloramphenicol may be used
  • Sulfonamides ↑ severity of infection
  • Penicillin derivatives ineffective
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21
Q

Rocky Mountain Spotted Fever

Etiology and Transmission

A
  • Causative Agent - R. Rickettsii
  • Reservoir - lower animals, birds
  • Vector - Wood tick (Dermacentor adersoni), dog tick (Dermacentor variabilis)
  • Distribution - The Rocky Mountain region, Eastern and Southeastern US
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22
Q

Rocky Mountain Spotted Fever

Clinical Disease

A
  • Transmission occurs via the bite of a tick
    • Individuals hiking, camping, fishing or picnicking in wooded areas are at risk
  • Incubation period of 3 to 12 days
  • Sudden-onset fever, chills, HA, malaise, myalgias (calf TTP)
  • Rash appears 2-4 days later
    • Involves the trunk as well as the soles and palms and can evolve from a macular to a petechial form
  • Sx and rash confusing in kids b/c childhood diseases w/ a rash may mimic RMSF
  • Complications include DIC, thrombocytopenia, encephalitis, vascular collapse, and renal and cardiac failure
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23
Q

Rickettsial Pox

Etiology and Transmission

A
  • Causative Agent: R. akari
  • Reservoir: House mouse
  • Vector: House mouse mite
  • Distribution: Occurs in large urban areas of the US as well as in Russia, Korea and other countries
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24
Q

Rickettsial Pox

Clinical Disease

A
  • Mild disease
  • Vesicular rash and local eschar w/ regional lymphadenopathy
  • Early sign ⇒ erythematous papules → vesicles → eschar
  • Systemic sx ⇒ chills, fever, malaise, headache and myalgia
  • Disease may be debilitating
  • No fatalities have been reported
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25
Q

Epidemic Typhus

(Louse-borne typhus)

Etiology and Transmission

A
  • Causative Agent: R. powazekii
  • Reservoir: humans, flying squirrels
  • Vector: human body louse (Pediculus humanus corporis)
  • Distribution: Central and South America, Africa
  • Epidemic typhus is transmitted from louse to man to louse, and therefore, thrives best under crowded conditions where poor hygiene exists
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26
Q

Epidemic Typhus

Clinical Disease

A
  • Incubation 1-2 weeks
  • Abrupt-onset sx
  • First headache, malaise and elevated temperature
  • Rash may develop 4-7 days after the onset of illness
    • Patchy cutaneous erythema → maculopapular, petechial or hemorrhagic forms
    • Rash usu. does not affect the sole of feet, palms or face but characteristically appears on the trunk first and then extends toward the extremities
  • Complications include myocarditis and CNS dysfunction
27
Q

Brill-Zinsser

Disease

A
  • Milder, recrudescent (reactivation) infection
  • Occurs in pts who had epidemic typhus many years ago (10-40 years)
28
Q

Endemic Typhus (Murinetyphus)

Etiology and Transmission

A
  • Causative Agent: R. typhi
  • Reservoir: rat
  • Vector: rat flea (Xenopsylla cheopsis)
  • Distribution - endemic in many countries
  • Occurs in the Southeast and Gulf Coast region of US
29
Q

Endemic Typhus

Clinical Disease

A
  • Gradual-onset of fever, headache, malaise, myalgia
  • Skin rash ⇒ trunk → extremities
  • Disease is usu. mild
  • Fatalities usu. occur among the old and infirm
30
Q

Scrub Typhus

(Tsutsugamushi Disease)

Etiology and Transmission

A
  • Causative AgentOrientia tsutsugamushi (previously known as R. tsutsugamushi)
  • Reservoir - rodents
  • Vector - mites of which the larval stage (chigger) is the only stage that feeds on vertebrates
  • Distribution - Japan, Australia, Vietnam, Korea and India
31
Q

Scrub Typhus

Clinical Disease

A
  • ~ 3 wks after being bitten ⇒ chills, fever and headache
  • Skin rash develops
    • Characterized by a local cutaneous lesion ⇒ vesicular lesion → eschar (black scab covered sore)
  • Up to 30% mortality in untreated cases
  • Fatalities in treated cases rare
32
Q

Ehrlichiosis

Etiology and Transmission

A
  • Causative agents
    • Ehrlichia chaffeensis (human monocytic ehrlichiosis)
    • Ehrlichia ewingii, Anaplasma phagocytophilum (human granulocytic ehrlichiosis)
  • Reservoir: cattle, domestic animals, dogs
  • Vector: deer and dogs ticks (Ixodes scapularis, Amblyomma americanum, D. Variabilis)
  • Distribution: SE, mid-Atlantic, South and Central areas of the US
33
Q

Ehrlichiosis

Clinical Disease

A
  • Similar to RMSF
  • 10-12 days after a tick bite ⇒ fever, headache, malaise, and myalgia
  • Leukopenia d/t destruction of leukocytes
  • Thrombocytopenia develops
  • Rash is uncommon
  • Mortality 5-10% and mostly in the elderly
34
Q

Yersinia pestis

Overview

A
  • Yersinia pestis causes Bubonic and Pneumonic Plague
  • Today, 90% of plague occurs in SE Asia
  • In the USA, plague occurs primarily in the semi-arid plains
  • Focus in Arizona, New Mexico, Colorado, and Utah
35
Q

Yersinia pestis

Characteristics

A
  • Short gram-⊖ rods
  • Grow optimally at 28-30°C
  • Wright-Giemsa stain ⇒ exhibit bipolar staining
  • Facultative intracellular parasites of MΦ
36
Q

Yersinia pestis

Virulence

A
  • Capsular (F1 antigen) and cell wall (V-W antigens) antigens
    • Resistance to intracellular digestion by phagocytes
  • Secrete Yersinia outer proteins (Yops)
    • Anti-phagocytic, anti-inflammatory and toxic activities
    • Type III secretion system
    • Encoded on a virulence plasmid
37
Q

Yersinia pestis

Lifecycle and Transmission

A
  • Plague has two major cycles ⇒ sylvatic and urban
  • Human infections acquired:
    • By contact w/ infected rodents
    • By the bite of infected fleas
    • Respiratory transmission from man to man during pneumonic disease
38
Q

Bubonic Plague

Clinical Disease

A
  • Organisms invade lymphatics and infect regional lymph nodes
  • Produces a hemorrhagic suppurative necrosis ⇒ painful swelling called a bubo
    • Buboes occur 2-7 days after flea bite
  • W/o treatment, 50-75% of infected patients develop septicemialungs, liver, spleen and occasionally meninges
  • DIC may lead to death w/in hours or days of bubo development
39
Q

Pneumonic Plague

Clinical Disease

A
  • Primary pneumonic plague is highly contagious
  • Results from inhalation of infected droplets
  • Leads to hemorrhagic consolidation and sepsis
  • Death occurs after 2-3 days of illness
40
Q

Yersinia pestis

Laboratory Diagnosis

A
  • Gram stain, IF staining, and culture of bubo aspirate, blood or sputum
  • Serologic tests:
    • Agglutination
    • Complement fixation
    • Precipitation
41
Q

Yersinia pestis

Prognosis and Immunity

A
  • Mortality rate w/o treatment
    • Bubonic plague ~50%
    • Pneumonic plague nearly 100%
  • Recovery from bubonic plague confers long lasting immunity
    • Likely due both to opsonizing Ab and CMI
42
Q

Yersinia pestis

Treatment and Prevention

A
  • Streptomycin and gentamicin ⇒ drugs of choice
  • Formalin-killed vaccine developed for those exposed to high-risk environments
    • No longer available in the us
  • New vaccine using recombinant F1 and V antigens to induce protective Ab are in clinical trials
43
Q

Tularemia

Etiology

A

“Rabbit Fever, Rabbit Skinner’s Disease, Or Deerfly Fever”

  • Causative agent - Francisella tularensis
  • Reservoir - rabbits, squirrels, muskrats, beavers, deer
  • Vectortick, deer fly
44
Q

Francisella tularensis

Transmission and Distribution

A
  • Distributed throughout the Northern Hemisphere
  • ~ 200 cases/year in the US
  • Humans become infected by:
    • Direct contact w/ infected animals
    • Bite of an insect vector
    • Inhalation of aerosols
    • Ingestion of contaminated food or water
  • An infectious dose is only 50-100 organisms
45
Q

Francisella tularensis

Characteristics

A
  • Small, facultative, gram-⊖ coccobacillus
  • Fastidious
  • Requires sulfhydryl compounds for growth
  • Incubation for 2-10 days
46
Q

Francisella tularensis

Virulence

A
  • Encapsulated
  • Facultative intracellular pathogens
  • Able to resist intra-phagocytic killing
47
Q

Francisella tularensis

Pathogenesis

A
  • Infected tissue characterized by:
    • Invasion of MΦ
    • Necrosis
    • Granuloma formation
  • Clinical manifestations of disease depend on route of infection
48
Q

Tularemia

Ulceroglandular form

A
  • Most common
  • Ulcerating, necrotic papule develops @ site of infection w/in 2-6 days
  • ± Regional lymphadenopathy
49
Q

Tularemia

Glandular form

A
  • Usu. vector borne
  • Regional lymph node enlargement
  • Constitutional sx w/o any skin lesion ⇒ fever, headache, malaise
50
Q

Tularemia

Oculoglandular form

A
  • Painful, purulent conjunctivitis
  • Cervical and preauricular lymphadenopathy
51
Q

Tularemia

Typhoidal form

A
  • Most severe
  • Primary infection or secondary to other disease forms
  • Bacteremic spread of organism → lung, liver, kidney, spleen
  • Sx may include fever, weight loss, pneumonia
  • May mimic typhoid fever, brucellosis or tuberculosis
52
Q

Francisella tularensis

Laboratory Diagnosis

A
  • Culture requires special handling and media containing sulfhydryl compounds
  • Not routine in a clinical laboratory
  • Dx relies primarily on serology
  • Agglutination assays ⊕ in 2-4 weeks
  • Single titer ≥ 1:160 suggestive of F. Tularensis infection if H&P consistent
53
Q

Francisella tularensis

Treatment and Immunity

A
  • Streptomycin or gentamicin for 7-10 days
  • Naturally acquired infection confers long lasting CMI
  • Attenuated, partially protective vaccine available for persons w/ high risk of exposure
54
Q

Brucella

Overview

A
  • Medically important species ⇒ B. suis, B. melitensis, and B. abortus
    • In the USA, B. abortus most common followed by B. suis
  • Causes Brucellosis in man
    • Also known as undulant fever and Malta fever
    • Relatively rare disease is the US
55
Q

Brucella

Characteristics

A
  • Aerobic, short gram-⊖ rods (coccobacillary)
  • Catalase ⊕ and oxidase ⊕
  • Require complex media such as trypticase-soy agar and CO2 for cultivation
56
Q

Brucella

Virulence

A
  • Facultative intracellular parasites
  • May possess a small capsule
  • Possess endotoxin
  • No exotoxins or other specific virulence factors ID’d
57
Q

Brucella

Transmission

A

Brucella are transmitted to humans by accidental contact w/ infected animal feces, urine, milk and tissues

  • Routes of infection include:
    • Intestinal tract ⇒ ingestion of contaminated milk
    • Mucous membranes ⇒ droplets
    • Skin ⇒ contact w/ infected animals or contaminated animal tissues or products
  • Risks for infection:
    • Consumption of unpasteurized milk and milk products
    • Occupational exposure (farmers, slaughterhouse workers, veterinarians)
58
Q

Brucella

Pathogenesis

A
  • Enter and multiply w/in phagocytic cells
  • Spread from the site of infection via lymphatics → regional lymph nodes → bloodstream → seed a variety of organs and tissues
  • Granulomatous nodules and abscesses may develop in lymphatic tissue, spleen, kidney, liver, bone marrow
  • Granulomas consist of epithelioid and giant cells
    • See central necrosis and peripheral fibrosis
    • Caseation varies
      • Dependent somewhat on infecting species
59
Q

Brucellosis

Clinical Disease

A
  • Incubation period varies from 1-6 weeks
  • Onset is insidious w/ malaise, fever, weakness, aches and sweats
  • Characteristic intermittent or undulating fever w/ diurnal variation and a drenching night sweat
  • Lymph nodes are enlarged
  • Spleen becomes palpable
  • Acute sx may subside over weeks to months
  • Chronic stage may develop
    • Sx may include low grade fever, weight loss, myalgia, weakness, nervousness and other non-specific sx
60
Q

Brucella

Laboratory Diagnosis

A
  • Culture
    • Isolation of Brucella is difficult and time consuming
    • Subcultures made every few days for 4-5 weeks
  • Final ID by biochemical tests and agglutination assays
    • Specimens include blood and biopsy material (i.e. Liver, lymph node or bone marrow)
  • Serologic tests
    • Standard tube agglutination test is the most reproducible
    • 4-fold rise in agglutination titer is dx for Brucella infection
    • Single titer of 1:160 is presumptive e/o infection
    • ELISA
61
Q

Brucella

Treatment and Immunity

A
  • Intracellular location of Brucella makes treatment difficult
  • Combo of tetracycline w/ streptomycin or gentamicin for 4-6 weeks
  • Circulating bactericidal Abs may provide some resistance to subsequent attacks
    • Organisms are protected from Ab d/t intracellular location
  • Reinfections and/or persistence of infections common
  • CMI important for recovery from disease
62
Q

Pasteurella multocida

Characteristics

A
  • Small gram ⊖ coccobacilli
  • Grow as small, non-hemolytic mucoid colonies on blood agar
  • Normal flora of respiratory and GI tracts of various animals including cats and dogs
63
Q

Pasteurella multocida

Infections

A
  • Common cause of infection after bite or scratch from a dog or cat
  • Diffuse cellulitis w/ a well-defined erythematous border develops @ site of infection
  • Chronic abscess may develop in some cases