L 82-83 Viral Hemorrhagic Fevers Flashcards
General charactersitics of VHF viruses
Enveloped RNA viruses
Animal or arthropod hosts
Transmission generally arthropod vector or contact with rodent excretions
Person-person transmission low
Geographically restricted to where the host species lives
Prevention depends on control of animal/insect host/vector
Treatment is often supportive
Shared features among VHF’s
Fever and other noon-specific Sx Hemorrhagic Thrombocytopenia Shock Neuro disturbances
Initial SSx:
Fever, fatigue, dizziness, myalgia, weakness, exhastion
More serious: bleeding under skin, internal organs or from body orifices, coma, delirium, seizures
General pathogenesis of VHF’s
Virus initially infects macrophages and dendritic cells causing cytokine release. These might include gamma interferon, IL-1,6, TNF-alpha
Cytokines cause inflammatory response and coagulation pathways
Dendritic cells reduce expression of co-stimulatory molecules that are needed for T-cell activation => decreased immune response
What is the cause of the bleeding in VHF’s?
Multifactorial cause: Hepatic damage Coagulation dysregulation Thrombocytopenia Increased vascular permeability
What are the 4 main virus families in VHF’s?
Flaviviridae
Bunyaviridae
Arenaviridae
Filoviridae
Flaviviruses features and most common viruses in this group causing hemorrhagic fever
Dengue and Yellow fever
(+) sense enveloped RNA
Dengue Fever Epidemiology
Tends to be in more tropical areas but is spreading
Four serotypes: DENV-1-4, no cross-immunity
Natural host: primates, but humans are now being considered also
Transmission: Aedes aegypti mosquito
Dengue clinical features
Acute infection
Characterized by high fever and at least 2 of:
Severe headache, eye pain, joint pain, muscle/bone pain, rash, mild bleeding, low WBC or platelets
Resolves in 1-2 weeks
Dengue hemorrhagic fever
Usually after infection with a second dengue fever
High fever, hemorrhagic manifestations, thrombocytopenia, plasma leaking, pleural effusion, ascites
Explain why a second infection from dengue is worse than the first
In the first infection, there is production of neutralizing and non-neutralizing antibodies to the virus. The neutralizing antibodies remove the infection and the person recovers.
In the second infection, there is already present many antibodies that are non-neutralizing. They bind to the virus and promote uptake into macrophages and dendritic cells which actually helps the proliferation of the virus.
Enhanced uptake causes the macrophages to release cytokines, and the cells also signal memory T cells to release cytokine => increased vascular permeability
The immune complexes join with platelets and cause coagulation
Detection of dengue
Viral RNA and NS1 antigen can be detected early
IgM early, IgG later
Dengue prevention
There is now a vaccine available called Dengvaxia–live-attenuated and tetravalent
Approved for use in other countries
Yellow Fever epidemiology
Two strains: Dakar and 17D
Africa and South America
Host: primate, but now humans also
Vector: Mosquito–aedes, haemagogus, sabethes
Yellow fever clinical manifestations
Biphasic disease:
Acute Phase: fever, myalgia with backache, HA, loss of appetite, N/V, red tongue, skin flushing, red eyes, Sx fade in 3-4 days
Toxic Phase: in 15-20% of patients, return of fever, bradycardia, jaundice, GI hemorrhage, abd pain, dissemination to kidneys, heart, vasculature causing widespread hemorrhaging, can be fatal
Yellow Fever pathogenesis
Similar to Dengue in many ways
Attacks Kupffer cells and hepatocytes
Councilman bodies in liver biopsy
Yellow Fever immunity
Live-attenuated vaccine against 17D strain, single vaccine sufficient immunity
Characteristics of Bunyaviruses
Enveloped, (-) sense RNA
Three segments in genome: L, M, S
Viruses causing hemorrhagic fevers:
Phlebovirus
Nairovirus
Hantavirus
Rift Valley Fever Epidemiology
Eastern and Southern Africa
Mosquito transmission
Also transmitted by contact with infected animal tissues or secretions–livestock
Rift Valley Fever clinical features
Typically asymptomatic or mild assoc. with fever and liver illness
Can mimic influenza
Can have hemorrhagic manifestations–shock, encephalitis, ocular disease, hepatic necrosis, blindness
Rift Valley Fever Pathogenesis
Replication in RES cells at site of bite or contact
Viremic spread to other tissues and organs