Hemorrhagic Viruses Flashcards
What Hemorrhagic disease might you suspect if your pt. had just traveled to Central or South America?
- Yellow Fever
* Arenavirus
What Hemorrhagic disease might you suspect if your pt. had just traveled to West Africa?
• Lassa Fever
What Hemorrhagic disease might you suspect if your pt. had just traveled to Central Africa?
- Ebola
- Marburg
- RVF
- CCHF
Flaviviridae
• Genomic structure and Packaging
• Important viruses caused by this pathogen
Genome: • Small • Non-Segmented • +ssRNA • Enveloped
Diseases Caused:
• Dengue Virus*
• Yellow Fever Virus*
• Hep C
Describe the Replication Cycle of Dengue and Yellow Fever Viruses.
Flavivirdae
Entry:
• pH Dependent
- +ssRNA translated by host ribosome to make RNA-dep.-RNA-pols.
- RNA-dep.-RNA-pols copies genome and Structural Prots. are made and capside is assembled
- Capside BUDS through the Goli or ER and then out of the Cell
How is the Flavivirus transmitted?
• diseases that it causes
• Prevalence
Diseases: Dengue Virus, Yellow Fever Virus
INSECT VECTORS:
• ARBOviruses (anthropod-borne virues)
Dengue is 2nd only to Malaria in importance of Tropical Diseases
What organs do Dengue and Yellow Fever infect?
• Primary and Secondary Viremia
Primary Viremia: Insect bite puts the virus into the epithelium and it becomes established then transmits to • Macrophages • Spleen • Lymph Node
Secondary Viremia:
Happens in Immunocompromised ONLY
• Hemorrhagic Fever and Shock Ensue
Where are you most likely to acquire a Dengue Fever Virus (DFV)?
- South America
- Southeast Asia
- Africa
***Note: most cases of dengue in America have been acquired abroad
Classic Dengue Virus • Incubation Period • Characteristic Symptoms (early?, late?) • Lab Values • Recovery
Incubation Period:
• 2-7 days
Early:
• Mottled Rash on day 1 or 2
• Metallic Taste in their mouth
Later:
• Myalgia
• Increased Muscle and Joint pain (Bonebreak Fever)
Lab Value:
• LOW PLATELETS less than 100x10^9/L
Recovery:
• Slow (~2 weeks post inf. recovery)
Dengue Hemorrhagic Fever (DHF) • WHO criteria for Dx. • Characteristic Symptoms (early?, late?) • Lab Values • Recovery
Dx: • Fever • Hemorrhagic symptoms (thrombocytopenia, etc) • Circulatory Failure (hypoproteinurea) • Hepatomegaly
Early:
• Abdominal Pain
• Restlessness and Change in Mental Status
• CAPILLARY LEAKAGE
Late (untreated):
• Progression to Dengue Shock Syndrome preceded by vomiting and restlessness
*shock is caused by capillary leakage causing hypovolemia and acidosis in lowly perfused tissues
What is suggested by the fact that in greater than 90% of Fatal DHF cases the person had previously been infected with a different Dengue Virus?
*Immune-mediated pathology initiates the events that cause the hemorrhagic syndrome
T or F: you need laboratory conformation to diagnose someone with DHF.
True, this is because the symptoms are so non-specific
How do you use lab tests to confirm a Dengue infection?
Serodiagnosis:
• 4 fold rise in antibody titer in paired IgG or IgM specimens
Other Methods:
• Culture
• RT-PCR
How should you avoid Dengue Infection?
Avoid Getting bit by mosquitoes
There is now a tetravalent dengue vaccine approved for use in Mexico, Brazil, and the Phillippines containing recombinant capsid proteins, it effective but not approved for use in children under 9
There is now a tetravalent dengue vaccine approved for use in Mexico, Brazil, and the Phillippines containing recombinant capsid proteins, it effective but not approved for use in children under 9
Where are you most likely to get infected with Yellow Fever?
*South and Central America as well as Africa
What is the difference between Jungle, Savannah, and Urban Yellow Fever Virus?
• Found where?
Jungle (S. America or Africa)
• Transmitted from monkey to man via mosquito - found in workers and ppl. who visit the jungle
Savannah (Africa only)
• Transmitted from monkey or man to monkey or man - found in workers and ppl. who live or work on the border of the jungle
Urban (Anywhere)
• Transmitted from human to human only
What is the major Vector in Urban Yellow Fever?
Aedes aegypti
What are some symptoms of Yellow Fever?
• Death rate
• Prevention
- Black Vomit
- Jaundice from SEVERE liver damage
Death Rate = 20%-50% 7 to 10 days post infection mostly due to Hepatorenal Failure
Prevention:
• Live Attenuated Vaccine Can be Used
What viruses do you need to know that can be transmitted by mosquitoes?
Denque and Yellow Fever
How would you diagnose yellow fever?
- Isolation and Incubation of Virus
- Serologic Identification via ELISA or IgG or IgM
- RT-PCR
Bunyaviridae
•genome type
• Structure/Shape
• Enveloped?
3 Main types
Bunyaviridae
• -ssRNA with Segmented Genome
• Enveloped
Types:
• Rift Valley Fever Virus
• Crimean-Congo Virus
• Hantavirus (aka HFRS - hemorrhagic fever with renal syndrome)
How are the 3 different types of Bunyaviridae transmitted?
• where are they typically found
Africa
• Rift Valley Fever Virus - Mosquitos
Africa-Middle Ease
• Crimean-Congo Virus - Ticks
Asia and Europe
• Hantavirus (aka HFRS - hemorrhagic fever with renal syndrome)
Steps in Replication of Bunyaviridae Viruses?
- pH dependent endocytosis
- Uncoating releases Viral RNA-dep. RNA-pols. (RdRP) to make +ssRNA from the original -ssRNA genome
- Structural Proteins are made
- RdRP from virus make +cRNA from which 3 segments of -ssRNA can be transcribed and packed into nucleocapside
- Virus leaves by budding
Rift Valley Fever Virus
• Primary Importance and endemic region
• Vector
• Prevention
**subtype of Bunyviridae Rift Valley Fever Virus Primary Importance: • Causes disease in livestock on AFRICA causing abortions etc. • Could be used in bioterrism
Vector:
• Mosquito (for animals)
• Animal Blood and Organs Etc. (for humans)
Prevention:
• Immunize the damn animals
Rift Valley Fever Virus
• Progression
• Symptoms
• Treatment
**subtype of Bunyviridae
Progression:
• Acute, Self-Limiting with Mild Fever
• 2% progressed to Hemorrhagic Hepatitis
Most Common Symptoms:
• Fever
• Encephalitis
• Retinal Vasculitis (causing blindness)
*No Established Treatment
What disease is severe Rift Valley Fever Virus often confused with?
• why?
Severe manifestations are confused for meningitis because it causes stiff neck, photophobia, and vomitting
Crimean-Congo Hemorrhagic Fever Virus • Transmission • subtype of? • Endemic to? • Symptoms? • Severity, targeted organs?
Transmission:
• Ticks
Subtype of Bunyviridae
Endemic to Africa, Middle East, Europe
Symptoms
• Headache
• Pain in Limbs
• Bleeding from many orifices
Severity:
• Really Bad, Targets Liver and Vascular Endothelium
• 30% mortality
Hemorrhagic Fever with Renal Syndrome aka Hantavirus • Transmission • subtype of? • Endemic to? • Symptoms? • Severity, targeted organs?
Transmission
• Rodents via urine, droppings, nests
Subtype of Bunyviridae
Endemic to Europe and Asia
Symptoms
• Develop 1 to 2 weeks post exposure
• Fever, Hemorrhage
• Acute Renal Failure
Severity:
• Liver and Vascular Endothelium Targeted, over 15% mortality rate
Adrenaviridae • Enveloped? • Genome structure • Unique feature • Transmission
Genomic Info.
• Enveloped
• Segmented AMBIsense RNA virus
• Virions often carry host cell ribosome
Transmission:
• Rodent Excreta (pee, shit, dust etc.)
What 2 major forms of Arenaviridae exist?
• Found where?
Old World:
• Lassa Fever Virus
• AFRICA
New World:
• South American Hemorrhagic Fever Viruses
Arenavirus Replication
pH depedent endocytosis
AMBISENSE STRATEGY FOLLOWED
• 2 stands Long and Short are transcribed into NP and L mRNA
• Each NP and L segment is copied into an antigenome
• the (+) -sense antigenome is used as a template to transcribe glycoprotein mRNA
Virus Particles are released by Budding
Arenavirus • transmission • Infection Severity • Vaccine? • Medications?
Transmission:
• Via inhalation of aerosolized virues form rodent excreta and saliva
Infection Severity:
• Mild or Subclinical
• 5-10% of total infections are Severe and Multisystem
Vaccines:
• No vaccines are currently available
Meds:
Ribaviron
How does the mild form of Arenavirus present?
• Severe presentation?
• Lab values in severe stage?
Mild:
• Fever, Weakness, Malaise, Lumbar Pain, Cough
• Severe Headache
Severe:
• Prostration
• Facial or Neck Edema
• Abdominal Pain
Lab Values:
• Lymphopenia
• Thrombocytopenia
• Qualitative Defects in Platelet Function
Filoviridae
• Genome Structure
• Enveloped?
• 2 subtypes
Genome Structure:
• Nonsegmented, -ssRNA
• Enveloped
2 subtypes:
• Marburgvirus
• Ebolavirus
Devastating Hemorrhagic Shock induced in both human and primates
Ebolavirus Transmission Routes
- Bodily Fluids (literally any type)
* Fruit Bats (reservoir)
**Pathogenesis of Filovirus
• Initial Target of Infection
Initial Target
• Macrophages and Monocytes = Initial Target
• causes a CYTOKINE STORM
Next:
• Liver, Kidney, and Spleen host a ton of virus production
• LOSS OF PLATELETS AND OTHER IMMUNE CELLS HERE LEADS TO THE HEMORRHAGIC HALLMARK
Finally:
• Mucosal Surfaces begin to hemorrhage
• Brain, Spleen, and Lymph nodes begin to swell
T or F: the lesions created on organs by Filovirus (ebola) contain MASSES of virus nucleocapsid
True
Ebola (filovirus)
• Early Symptoms
• Late Symptoms
• Cause of Death
Early:
• RAPID onset flu-like symptoms (fever, myalgia, headache, vomiting)
• Macoulopapular Rash
Late:
• Hemorrhagic Shock
Cause of Death:
• HYPOVOLEMIC SHOCK and Systemic Organ Failure
How long is the incubation period for Ebola?
4-10 days, but can be as many as 21
How is Ebola treated?
Goal - Keep the Patient Alive so they can mount an Immune Response
• Fluid and Electrolyte Replacement
• Supportive Care
T or F: our bodies can mount a robust immune response to Ebola.
True, this is done with a NEUTRALIZING antibody that is so good, we can transfuse it into ill pts. and they may survive
T or F: there are currently 2 FDA approved treatments/vaccines available against ebola.
False, ZMapp and Ebola vaccines were used in the last outbreak, but are not FDA approved
What does ZMapp consist of?
3 mouse-human chimeric mAbs that neutralize the virus
