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
Rift Valley Fever immunity
Long-lasting immunity
Vet vaccines available
Not developed for humans
Crimean-Congo Hemorrhagic Fever Epidemiology
SE Europe, Asia, Africa
Vector and Reservoir: Tick
Crimean-Congo Hemorrhagic Fever clinical features
Early: fever, HA, severe back, joint, abd pain, vomiting, flushing, red eyes
Later: Hemorrhages–petechia, purpura, ecchymoses, subconjunctival, mucosal membranes; Pulmonary edema and shock, hepatitis, liver and kidney failure
Crimean-Congo Hemorrhagic Fever pathogenesis
Similar to Dengue in replication at bite site and spread to other organs and tissues
Hantaan virus Epidemiology
Considered an old world virus
China, E. Russia, Korea
Causes Korean hemorrhagic fever or Hemorrhagic Fever with Renal Syndrome
Reservoir: striped field mouse
Infection: contact with infected rodent tissues or secretions
Hantaan (HFRS) clinical features
Early: F/C, HA, flushing, low back pain, abd pain, N/V/D, blurred vision, hemorrhages–petechia, purpura, subconjunctival, thrombocytopenia
Later: Low BP, vascular leakage, edema, renal dysfunction, shock
Hantaan (HFRS) Pathogenesis
Virus replicates similar to RVF in RES cells and spreads throughout body, especially to the kidneys
Hantavirus Epidemiology
New world virus–Americas
Causes Hantavirus Pulmonary Syndrome (HPS)
Sin Nombre Virus (many others exist)
Host: deer mouse
Infection: by contact with rodent secretions–stool, urine, saliva
Also from eating foods contaminated by infected mice
Hantavirus (HPS) Clinical Features
Early: 1-5 weeks after infection, fever, fatigue, muscle aches, HA, dizziness, chills, abd Sx
More serious: cough, SOB, tachycardia, tachypnea, pulmonary edema=ards
Sin nombre virus Pathogenesis
Infection through respiration of airborne particles from infected rodents
Does not cause hemorrhagic symptoms
Characteristics of Arenavirus
Enveloped ambisense ssRNA viruses
Segmented genome–2: L and S
Many viruses, cover Lassa virus here
Lassa virus epidemiology
First seen in Nigeria
Reservoir: rat
Transmitted: ingestion of contaminated urine or feces, or direct contact with rat, can transfer person-person
Lassa clinical features
Initially: insidious onset, fever, malaise, myalgia, retrosternal pain, cough, sore throat, severe headache, nausea vomiting
Severe: exhaustion, facial edema, neuro–tremors, seizures, coma, deafness; hemorrhagic in skin and mucous membranes, multiple organ necrosis, shock
Lassa Pathogenesis
Acquired through inoculation, inhalation, ingestion from infected rat
Virus infects endothelial cells and macrophages causing cellular and vascular damage as well as release of inflammatory mediators
Characteristics of Filoviruses
Single genome, filamentous looking virion
Includes Ebolavirus, Marburgvirus
Both cause severe and often fatal hemorrhagic fevers
Sx similar for both
Marburg epidemiology
Endemic to Africa
Fruit bats likely reservoir
Transmission: likely contact with secretions or tissues, human to human possible
Ebola epidemiology
Endemic to Africa
Five subtypes
Reservoir: fruit bat
Transmission: likely contact with secretions or tissues, human to human possible
Filovirus clinical features
Severe to fatal hemorrhagic fever
Early: HA, fatigue, fever, myalgia,
Later: sudden high fever, vomiting blood, passive behavior, bruising, brain damage, bleeding nose and mouth, LOC, seizures, massive internal bleeding, death within week of onset of symptoms
Bleeding form thrombocytopenia and vascular damage
Filovirus Pathogenesis
Virus replicates rapidly in blood stream causing extensive necrosis in liver, adrenal, spleen, lymph, lungs, endothelium, etc.
Macrophages release mediators that mimic shock causing widespread hemorrhage => DIC, edema, hypovolemic shock
Diagnosis of VHF and HPS
Geographic
Serology
PCR
Lab findings
Treatment of VHF and HPS
Supportive care
Ribavirin shown to be helpful in some
ZMapp for Ebola
Preventing VHF and HPS
Vaccines for Yellow Fever and Dengue, patient isolation, rodent control
Patient has been to Korea, contact with a striped field mouse, and has renal dysfunction
Disease?
Hemorrhagic fever with renal syndrome (HFRS)
Hantaan virus
Patient from E/S Africa, bit by mosquito that has been feeding on livestock, ends up with blindness
Disease?
Rift Valley Fever
Patient from SE Europe, is bitten by a tick
Disease?
CCHF
Crimean-Congo Hemorrhagic Fever
Patient bit by mosquito that has been feeding on monkeys, found to have the NS1 antigen, has hemorrhagic symptoms, and can progress to shock
Dengue fever
Patient in africa or south america, bit by mosquito after feeding on monkeys, jaundice, black vomit and councilman bodies found
Yellow Fever
Patient in Africa
Contacted fruit bat secretions, rapid course, extensive tissue necrosis
Marburg or Ebola
Patient in West Africa, disease from a rat, causes cough, sore throat, deafness
Lassa virus
Patient in North America, deer mouse infection, pulmonary edema, ARDS, no hemorrhagic manifestations
Sin nombre virus
Hantavirus Pulmonary Syndrome
