Bacterial Zoonotics Flashcards
Category A or Tier 1
Diseases/Agents
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)
Category B Diseases/Agents
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
Category C Diseases/Agents
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
Bacillus anthracis
Characteristics
- Aerobic
- Large, Non-Motile
- Gram-⊕ Rods
- Spore-formers
- Animal products contaminated w/ anthrax spores include hides, bristles, hairs, wool and bone

Bacillus anthracis
Spores
- Resistant to adverse chemical and physical environmental changes
- Withstand dry heat and certain disinfectants
- May persist in soil for years

Bacillus anthracis
Virulence Factors
-
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
-
Protective antigen (PA)
Bacillus anthracis
Pathogenesis
- 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
Anthrax Disease
- 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

Cutaneous Anthrax
- 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

Inhalation Anthrax
“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

Gastrointestinal Anthrax
“Ingestion Anthrax”
- Common in animals
- Rare in humans
- Infection in humans result in abdominal pain, N/V, and bloody diarrhea

Anthrax
Laboratory Diagnosis
- 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

Antrax
Treatment and Immunity
-
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
Rickettsiae
Morphology
- 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

Rickettsiae
Host Dependence
- 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
Rickettsiae
Virulence
- Multiply in endothelial cells of blood vessels
- Causes endothelial proliferation and perivascular infiltration ⇒ leakage and thrombosis
- Vasculitis particularly evident in small blood vessels in major organ systems
Rickettsiae
Immunity
- Opsonizing Ab and phagocytosis play a role in clearing Rickettsiae from the bloodstream
- Organisms are intracellular ⇒ cell-mediated immunity may also contribute
Rickettsiae
Culture
- 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
Rickettsiae
Laboratory Diagnosis
- 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
Rickettsiae
Treatment
- Doxycycline, tetracycline, or chloramphenicol may be used
- Sulfonamides ↑ severity of infection
- Penicillin derivatives ineffective
Rocky Mountain Spotted Fever
Etiology and Transmission
- 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

Rocky Mountain Spotted Fever
Clinical Disease
-
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

Rickettsial Pox
Etiology and Transmission
- 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

Rickettsial Pox
Clinical Disease
- 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

Epidemic Typhus
(Louse-borne typhus)
Etiology and Transmission
- 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
Epidemic Typhus
Clinical Disease
- 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
Brill-Zinsser
Disease
- Milder, recrudescent (reactivation) infection
- Occurs in pts who had epidemic typhus many years ago (10-40 years)
Endemic Typhus (Murinetyphus)
Etiology and Transmission
- 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
Endemic Typhus
Clinical Disease
- Gradual-onset of fever, headache, malaise, myalgia
- Skin rash ⇒ trunk → extremities
- Disease is usu. mild
- Fatalities usu. occur among the old and infirm
Scrub Typhus
(Tsutsugamushi Disease)
Etiology and Transmission
- Causative Agent – Orientia 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

Scrub Typhus
Clinical Disease
- ~ 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

Ehrlichiosis
Etiology and Transmission
-
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

Ehrlichiosis
Clinical Disease
- 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
Yersinia pestis
Overview
- 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

Yersinia pestis
Characteristics
- Short gram-⊖ rods
- Grow optimally at 28-30°C
- Wright-Giemsa stain ⇒ exhibit bipolar staining
- Facultative intracellular parasites of MΦ

Yersinia pestis
Virulence
- 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
Yersinia pestis
Lifecycle and Transmission
- 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

Bubonic Plague
Clinical Disease
- 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 septicemia ⇒ lungs, liver, spleen and occasionally meninges
- DIC may lead to death w/in hours or days of bubo development

Pneumonic Plague
Clinical Disease
- 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

Yersinia pestis
Laboratory Diagnosis
- Gram stain, IF staining, and culture of bubo aspirate, blood or sputum
- Serologic tests:
- Agglutination
- Complement fixation
- Precipitation
Yersinia pestis
Prognosis and Immunity
- 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
Yersinia pestis
Treatment and Prevention
- 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
Tularemia
Etiology
“Rabbit Fever, Rabbit Skinner’s Disease, Or Deerfly Fever”
- Causative agent - Francisella tularensis
- Reservoir - rabbits, squirrels, muskrats, beavers, deer
- Vector – tick, deer fly

Francisella tularensis
Transmission and Distribution
- 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

Francisella tularensis
Characteristics
- Small, facultative, gram-⊖ coccobacillus
- Fastidious
- Requires sulfhydryl compounds for growth
- Incubation for 2-10 days

Francisella tularensis
Virulence
- Encapsulated
- Facultative intracellular pathogens
- Able to resist intra-phagocytic killing
Francisella tularensis
Pathogenesis
- Infected tissue characterized by:
- Invasion of MΦ
- Necrosis
- Granuloma formation
- Clinical manifestations of disease depend on route of infection

Tularemia
Ulceroglandular form
- Most common
- Ulcerating, necrotic papule develops @ site of infection w/in 2-6 days
- ± Regional lymphadenopathy
Tularemia
Glandular form
- Usu. vector borne
- Regional lymph node enlargement
- Constitutional sx w/o any skin lesion ⇒ fever, headache, malaise
Tularemia
Oculoglandular form
- Painful, purulent conjunctivitis
- Cervical and preauricular lymphadenopathy
Tularemia
Typhoidal form
- 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
Francisella tularensis
Laboratory Diagnosis
- 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
Francisella tularensis
Treatment and Immunity
- 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
Brucella
Overview
- 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
Brucella
Characteristics
- Aerobic, short gram-⊖ rods (coccobacillary)
- Catalase ⊕ and oxidase ⊕
- Require complex media such as trypticase-soy agar and CO2 for cultivation
Brucella
Virulence
- Facultative intracellular parasites
- May possess a small capsule
- Possess endotoxin
- No exotoxins or other specific virulence factors ID’d
Brucella
Transmission
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)
Brucella
Pathogenesis
- 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

Brucellosis
Clinical Disease
- 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

Brucella
Laboratory Diagnosis
-
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
Brucella
Treatment and Immunity
- 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
Pasteurella multocida
Characteristics
- 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

Pasteurella multocida
Infections
- 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