Agents of bioterrorism II Flashcards
What are the characteristics of bacillus?
Gram +
Aerobic or Facultatively Anaerobic
Spore forming rods
Most species are opportunistic pathogens of low virulence
Two species cause disease: cereus (food poisoning) and anthracis (anthrax)
How does spore-forming ability help bacillus?
Spores are formed in soil and are very resilient and infectious
- Heat resistance
What are the virulence factors of Bacillus anthracis?
Capsule: poly D-glutamic acid
(hallmark of anthracis)
Toxins:
Edema toxin = EF+PA
Lethal toxin = LF+PA
PA = protective antigen = B subunit (cell binding component) for both toxins
–> anti-PA Abs neutralize toxins
What is Edema Factor?
A virulence factor of Bacillus anthracis
It is a calmodulin-dependent bacterial adenylate cyclase
What is Lethal Factor?
A virulence factor for Bacillus anthracis
It is a zinc-metaloprotease that cleaves mitogen activated protein kinase kinase (MAPKK) and inhibits MAPK signal transduction pathways in macrophages
*What makes anthrax lethal
What is the reservoir for Bacillus anthracis?
Reservoir: Soil
–> Herbivores infected during grazing
- Human transmission by:
Contact with infected animals, hides, hair, wool, bone, bone products, biting flies
Ingestion of contaminated meat
Inhalation
What are the forms of anthrax?
Cutaneous - most common in nature
Gastrointestinal
Inhalation - Woolsorter’s disease, bioterrorism
What is the presentation of cutaneous anthrax?
Produces a papule that progresses to central necrosis to black eschar
- Painless
- Edema occurs
- 80-90% complete resolution
What is the presentation of GI anthrax?
RARE!
- Follows ingestion of spore-contaminated meat
- Ulcers form at site of invasion (i.e. mouth, esophagus, intestine) which leads to
Regional lymphadenopathy
Edema
Sepsis
Mortality >50%
What is the presention of inhalational anthrax?
Non-specific symptoms for 3-5 days
Terminal phase:
Dyspnea
Stridor
Cyanosis
Increased chest pain
Chest wall edema
Shock and death within 24-36hrs
Hemorrhagic mediastinitis, hemorrhagic pleural effusions (seen on CXR)
- Can cause meningitis and GI hemorrhage
What is the CDC treatment for inhalational anthrax?
Combination Abx Therapy:
Ciprofloxacin or Doxycyclin
+
Clindamycin
+
Rifampin
What are the characteristics of Yersinia pestis?
Agent of bubonic plague
Gram - rod
Grows well on MacConkey’s agar
Flea vector requried for transmission
(exception: pneumonic plague)
What is the pathogenesis of Yersinia?
Flea bites and regurgitates bacteria –> Vesicular lesions at bite site –> Organism is phagocytosed by PMNs and Monocytes
Either Killed in PMNs
or
Released from monocytes
–> can now resist phagocytosis by both PMNs and monocytes –> goes to lymphatics –> localizes in regional lymph nodes and creates bubo
May Disseminate to bacteremia (–> pneumonia, meningitis, and/or septic shock)
or
Stop
How is plague diagnosed?
Culture on MacConkey’s agar or sheep blood agar
Drops of bubo aspirate, blood, or other materials used for staining
- -> Gram stain shows PMNs and Gram- coccobacilli
- -> Wayson stain shows light blue bacilli wiht dark blue polar bodies
What makes a virus a High priority for biodefense agent?
Pose a risk to national security because they:
- Can be easily disseminated or transmitted person-to-person
- High mortality
- Might cause public panic and social disruption
What is hemorrhagic fever?
Acute febrile illness characterized by malaise, myalgia, and prostration dominated by general abnormalities of vascular permeability, and regulation.
Bleeding manifestations often occur, usually diffuse and reflect widespread vascular damage rather than life-threatening volume loss
What are the virus families containing VHF agents?
Arenaviruses:
Lassa fever
S. American Hemorrhagic fevers
Bunyaviruses:
Congo-crimean hemorrhagic fever (CCHF)
Rift Valley Fever (RVF)
Hantaviruses
Filoviruses:
Ebola
Marburg
Flaviviruses:
Yellow-fever
Kyasanur Forest disease
Omsk hemorrhagic fever
What are the properties of Viral Hemorrhagic Fevers?
All enveloped, DNA viruses
- Survival is dependent on animal or insect reservoir
- -> Human infection is incidental to interaction with host
- Outbreaks occur sporadically and irregularly
- No cure or established drug treatment
What are key factors in the patient history of viral hemorrhagic fever?
Foreign travel to endemic or epidemic area
Rural environments
Possible nosocomial exposure
Contact with arthropod or rodent reservoir
Domestic animal blood exposure
What is the treatment for viral hemorrhagic fever?
Supportive care
Cautious sedation and anagesia use
Correct coagulopathies as needed
No anti-platelet drugs or IM injections!
Ribavirin possibly effective for:
Arenaviruses
Bunyaviruses
What are characteristics of Filoviruses?
Examples: Ebola and Marburg
Structure:
Pleomorphic
long, sometimes branched filaments
Shorter filaments shaped like a “6” or “U” or circles
- *Enveloped**
- *Single-stranded, negative-sense RNA**
New viral particles created by budding from surface of host cells (hence, enveloped)
What is the natural reservoir of ebola virus?
likely Bats
What are the subtypes of ebolavirus?
- Ebola-Zaire
- Sudan
- Ivory Coast
- Bundibugyo (causes disease in humans)
- Ebola-Reston (causes disease in non-human primates)
What is the natural reservoir for Marburg virus?
Fruit bats
How is Ebola virus transmitted?
By direct contact wiht blood and secretions of an infected person, and through contaminated needles, etc.
–> Nosocomial transmission occurs frequently during outbreaks
**There are no carrier states with Ebola virus - All infections are acute
How is Ebola virus diagnosed?
Difficult in early stages because of non-specific early symptoms (red eyes, skin rash, etc)
Early days: ELISA, IgM ELISA, PCR, virus isolation
Post-mortem: Immunohistochemistry, virus isolation, PCR
What are characteristics of Crimean-Congo Hemorrhagic fever?
Transmitted by ticks; responsible for severe outbreaks in humnas; not pathogenic for ruminants
Bunyavirus:
Genome is circular
Ambisense RNA (+ and -) in three parts:
Small (S), Middle (M), Large (L)
What are the Arenavirus hemorrhagic fevers in humans?
What are their characteristics?
Lassa fever and S. American hemorrhagic fever
Rodent-borne disease- contact with rodent excreta causes aerosol transmission
Enveloped virus
Grainy appearance caused by ribossomes from host cells
Ambisense RNA
What are characteristics of Lassa virus?
Arenavirus
Rodent reservoir (Mastomys species): transmitted through excreta inhalation, consumption, or bite
Secondary human-to-human transmission with occasional nosocomial outbreaks
- contact with blood or body fluids
Affects all ages and sexes; less sever in younger patients
Most serious in pregnant women (more susceptible and causes abortion)
What is the presentation of Lassa Virus?
Symptoms occur 1-3 weeks after infection:
Fever
Retrosternal pain
sore throat
Back pain
cough
Abdominal pain
Vomiting
Diarrhea
Conjunctivitis
Facial swelling
Proteinuria
Mucosal Bleeding
Hearing loss
Tremors
Encephalitis
- Due to varied, nonspecific presentation, clinical diagnosis is difficult
What is “Swollen Baby Syndrome”
Lassa fever in children and infants:
Edema
Abdominal Distention
Bleeding
Poor Prognosis
What is treatment for Lassa Fever?
Supportive!
Ribavirin: effective against Lassa
Hyperimmune serum: effects still uncertain although dramatic results have been reported
How is Lassa diagnosed?
ELISA to detect IgM and IgG antibodies as well as Lassa antigen
Culture
Immunohistochemistry on post-mortem diagnosis
How is lassa fever prevented?
No vaccine
Rodent control
What are characteristics of Hendra and Nipah viruses?
Paramyxoviruses
Zoonotic and highly pathogenic
Broad tropism: ephrin B2/B3 as receptors
BSL04 restricted
Glycoprotein spikes useful for Antibodies and may make vaccination a future possibility
What is the presentation of Nipah/Hendra infection?
Widespread, multisystemic vasculitis
- thrombosis, ischemia and necrosis
Most severe clinical and pathologic manifestations in brain, lungs, and spleen
Severe respiratory disease - “ARDS-like”
(pneumonitis/multi-organ failure and/or acute encephalitis)
What are characteristics of poxviruses?
Large (seen by light-microscope)
Outer lipoprotein envelope that encloses dumbell shaped core
Genome: Large, double-stranded linear DNA
Replicates in cytoplasm
Very resistant to inactivation viable in crusts for years at room temperature
What makes a virus suitable for eradication?
No animal reservoir
Lack of recurrent infections
One or few stable serotypes
Availability of an effective vaccine
Absence of subclinical infections
What are characteristics of Smallpox?
Disfiguring disease with high mortality
spread by secretions from mouth and nose and by material from pocks or scabs
Transmission requires close contact
Every vesicular lesion is at same stage (chickenpox and others have lesions at different stages at all times)
What is the distribution of smallpox lesion?
Denser on face, arms, hands, legs, and feet than body
Involvement of palms and soles
How is smallpox diagnosed?
Smear from lesions - stained with gentian violet; look for Guarnieri bodies
Electron microscopy of lesion material showing cytoplasmic inclusions and brick-shaped virions
Egg inoculation results in specific pock morphology on chorioallantoic membranes
PCR
What are complications from smallpox vaccine?
Generalized vaccinia
Eczema vaccinatum
Post-vaccination encephalitis
Progressive vaccinia
Overall fatality
