Bacterial Zoonotics Flashcards
(63 cards)
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)
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
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
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
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
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
-
Protective antigen (PA)
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
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
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
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
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
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
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
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
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
16
Q
Rickettsiae
Virulence
A
- 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
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
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
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
20
Q
Rickettsiae
Treatment
A
- Doxycycline, tetracycline, or chloramphenicol may be used
- Sulfonamides ↑ severity of infection
- Penicillin derivatives ineffective
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
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
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
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
25
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
26
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**
27
Brill-Zinsser
Disease
* Milder, recrudescent (reactivation) infection
* Occurs in pts who had epidemic typhus many years ago (10-40 years)
28
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
29
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
30
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**
31
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
32
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**
33
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
34
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**
35
Yersinia pestis
Characteristics
* **Short gram-⊖ rods**
* Grow optimally at 28-30°C
* Wright-Giemsa stain ⇒ exhibit **bipolar staining**
* **Facultative intracellular parasites of MΦ**
36
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_
37
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
38
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
39
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
40
Yersinia pestis
Laboratory Diagnosis
* **Gram stain, IF staining, and culture of bubo aspirate, blood or sputum**
* Serologic tests:
* Agglutination
* Complement fixation
* Precipitation
41
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
42
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
43
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**
44
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
45
Francisella tularensis
Characteristics
* **Small, facultative, gram-⊖ coccobacillus**
* Fastidious
* Requires sulfhydryl compounds for growth
* Incubation for 2-10 days
46
Francisella tularensis
Virulence
* **Encapsulated**
* **Facultative intracellular pathogens**
* Able to resist intra-phagocytic killing
47
Francisella tularensis
Pathogenesis
* Infected tissue characterized by:
* **Invasion of MΦ**
* **Necrosis**
* **Granuloma formation**
* Clinical manifestations of disease depend on route of infection
48
Tularemia
Ulceroglandular form
* Most common
* **Ulcerating, necrotic papule** develops @ site of infection w/in 2-6 days
* **± Regional lymphadenopathy**
49
Tularemia
Glandular form
* Usu. vector borne
* **Regional lymph node enlargement**
* **Constitutional sx w/o any skin lesion** ⇒ fever, headache, malaise
50
Tularemia
Oculoglandular form
* Painful, purulent conjunctivitis
* Cervical and preauricular lymphadenopathy
51
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
52
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
53
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
54
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
55
Brucella
Characteristics
* **Aerobic, short gram-⊖ rods (coccobacillary)**
* **Catalase ⊕ and oxidase ⊕**
* Require complex media such as trypticase-soy agar and CO2 for cultivation
56
Brucella
Virulence
* **Facultative intracellular parasites**
* May possess a **small capsule**
* Possess **endotoxin**
* No exotoxins or other specific virulence factors ID’d
57
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)
58
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
59
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
60
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
61
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
62
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
63
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
