Hemorrhagic Viruses Flashcards by Barrett Thompson

What Hemorrhagic disease might you suspect if your pt. had just traveled to Central or South America?

Yellow Fever

* Arenavirus

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What Hemorrhagic disease might you suspect if your pt. had just traveled to West Africa?

• Lassa Fever

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What Hemorrhagic disease might you suspect if your pt. had just traveled to Central Africa?

Ebola
Marburg
RVF
CCHF

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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

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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

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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

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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

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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

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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)

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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

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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

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T or F: you need laboratory conformation to diagnose someone with DHF.

True, this is because the symptoms are so non-specific

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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

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How should you avoid Dengue Infection?

Avoid Getting bit by mosquitoes

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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

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Where are you most likely to get infected with Yellow Fever?

*South and Central America as well as Africa

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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

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What is the major Vector in Urban Yellow Fever?

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Aedes aegypti

What are some symptoms of Yellow Fever?
• Death rate
• Prevention

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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?

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Denque and Yellow Fever

How would you diagnose yellow fever?

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Isolation and Incubation of Virus
Serologic Identification via ELISA or IgG or IgM
RT-PCR

Bunyaviridae
•genome type
• Structure/Shape
• Enveloped?

3 Main types

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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

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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?

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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

Hemorrhagic Viruses Flashcards

(44 cards)