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Virology 17 Viral agents of bioterrorism*

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In general, the term "viral hemorrhagic fever" is used to describe a
Severe multi-system syndrome
What system is characteristically damaged by Viral hemorrhagic fevers?
The vascular system
What are the five distinct virus families that make up VHF?
(FAB FP)
Filoviruses
Flaviviruses
Bunyaviruses
Paramyxoviruses
Arenaviruses
What is similar about the structure of the five arbovirus families that cause viral hemorrhagic fever?
They are all enveloped
RNA viruses
What test is positive in a patient with VHF?
Positive tourniquet test (petechiae form below tourniquet or BP cuff)
For which VHFs are vaccines available?
Argentine hemorrhagic fever (Junin virus)
Candid #1 is vaccine strain of Junin virus. Not licensed in US

Yellow fever virus
-Yellow fever 17D
Describe the VHF differential diagnosis
Bacterial
-Typhoid fever, rickettsioses (fever-rash), leptospirosis (vasculitis-hemorrhagic rash) meningococcemia (DIC)

Protozoa
Falciparum malaria – hemolysis-dark urine – “blackwater fever”

Others
Vasculitis, TTP, Hemolytic Uremic Syndrome, heat stroke
What type of viruses are Ebola and Marburg?
Ebola and Marburg are Filoviruses
Describe the Filovirus genome
Enveloped, single-stranded, negative-sense RNA
The natural reservoir of Ebola is:
Unknown (bats?)
Which group of rodent-borne viruses include LCMV, Lassa fever and S. American HFs?
Arenaviruses
Why do Arenaviruses have a grainy appearance?
Ribosomes
Describe the Arenavirus genome
2 strands of ‘ambisense’ RNA i.e. + and – strands together, S and L
How are Arenaviruses transmitted?
Aerosol
-Lassa and Machupo viruses are associated with secondary person-person and nosocomial transmission
How does Lymphocytic choriomeningitis present
LCM presents as aseptic meningitis or encephalitis: asymptomatic infection or mild febrile illnesses are the most common clinical manifestations
It is caused by Arenaviruses
What group of people are especially relevant to Lymphocytic choriomeningitis (LCMV)?
Pregnancy-related infection has been associated with abortion, congenital hydrocephalus, chorioretinitis and mental retardation; it is probably a greatly under-recognized cause of complications in pregnancy.
What features are characteristic of Lymphocytic choriomeningitis (LCM)?
A characteristic biphasic febrile illness:
Initial phase (a week) has fever, malaise, anorexia, muscle aches, headache.
A few days of remission, then⬦
Second phase - meningitis (fever, headache, and a stiff neck) or encephalitis (drowsiness, confusion, sensory disturbances, and/or motor abnormalities, such as paralysis).
Why would you rather not have Lassa fever?
Lassa fever is a significant cause of morbidity and mortality:
-80% of people infected subclinical or mild
-20% have a severe multisystem disease.
Also associated with occasional epidemics, during which the case-fatality rate can reach 50%.
How has Lassa fever affected Africa?
Endemic in portions of West Africa, 100,000 – 300,000 cases per year
5,000 fatal cases per year (hospital mortality is 15-60%)
What is the most common lasting complication of Lassa fever?
Deafness (1/3 cases)
For whom are the death rates from Lassa fever particularly high?
Women in the third trimester of pregnancy, and for fetuses (95% mortality)
How can Lassa fever affect babies?
“Swollen Baby Syndrome”
- Edema
- Abdominal distension
- Bleeding
- Poor prognosis
Prevention of Lassa fever depends on:
Rodent control
Why is an exciting night spent looking at Poxvirus relatively inexpensive?
Poxvirus can be seen by light-microscopy as a brick-shaped particle (230 x 400 nm)
What shape is the Poxvirus?
Complex (neither icosahedral nor helical)
Describe the Poxvirus genome
Double-stranded, linear DNA;
200 - 350 Kb. A DNA virus that replicates in the cytoplasm.
What are some random facts about Poxvirus?
Largest and most complex virus; very resistant to inactivation: viable in crusts for years at room temperature. Can be inactivated by UV light and chemical disinfectants.
What are the characteristics of Category A biological agents
High priority agents that pose a risk to national security because they:
Can be easily disseminated or transmitted from person to person
Result in high mortality, and have the potential for major public health impact
Might cause public panic and social disruption
Require special action for public health preparedness
What are the Category A diseases and agents
Anthrax ( Bacillus anthracis)
Botulism ( Clostridium botulinum toxin)
Plague ( Yersinia pestis)
Smallpox ( Variola Major)
Tularemia ( Francisella tularensis)
Viral Hemorrhagic fevers
-Filoviruses e.g. Ebola
-Arenaviruses e.g. Lassa fever
What are the characteristics of Category C biological agents
Emerging pathogens that could be engineered for mass dissemination in the future
Readily available
Easy to produce
Easy to disseminate
Potential for high morbidity and mortality with major health impact
What are the characteristics of Category B biological agents
Second highest priority agents include those that are moderately easy to disseminate, result in moderate morbidity rates and low mortality rates, and require specific enhancements of CDC's diagnostic capacity and disease surveillance
What are the characteristics of smallpox disease
Disfiguring disease with high mortality
Spread by secretions from mouth & nose and by material from pocks or scabs
Thus, transmission requires close contact with patients or their clothing or bedding
What is the progression of the smallpox rash
Appears 2-4 days after patient becomes ill with fever
Day #1
(few papules)
Day #2
(more papules)
Day #3
(beginnings of vesicles)
Day #4
(distinct vesicles;
firm to touch)
Day #5
(pustules;
fever returns)
Day #7
(obvious pustules)
Day #8 & 9
(increase in size;
firm to touch)
Day #10 to 14
(drying and scab formation)
Day # ~20
(scarring)
What is the distribution of rash in smallpox
Denser on face, arms, hands, legs, and feet than on body
Involvement of palms & soles
What is the distribution of rash in chickenpox
Denser on body, with fewer lesions on arms and hands
What are complications of Smallpox vaccination
Eczema vaccinatum
Postvaccinia encephalitis
Immunocompromised or pregnancy are contraindications for vaccine

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