Twenty Five Flashcards
What type of viruses are yellow fever and dengue? Envelope? Replication pattern?
Yellow fever virus and dengue virus are flaviviruses. They are enveloped, have a positive-
polarity single-stranded RNA, and encode one large polyprotein (see MHR syllabus Topics
Topic #15 for a review of general
virology). The overall structure,
genetic organization, and
intracellular replication of Yellow
Fever Virus and Dengue Virus are
similar to that of HCV (a non-
arboviral flavivirus discussed in
MHR Topic #17).
How is yellow fever spread? Location? What are its two infectious cycles? Main symptoms? Complications?
- Mosquito-borne
- Limited to tropical South/Central America & sub-Saharan Africa
- Two infectious cycles
- Jungle cycle (enzootic)
- Urban cycle (self-sustaining epizootic)
- This is the transmission mechanism for which the virus evolved. The virus
alternates its replication in mosquitoes and monkeys.
• Epizootic spillover from the enzootic cycle can occur when people enter the
jungle or are infected by mosquitoes on the edges of the jungle.
• Yellow fever virus is one of the few arboviruses that can replicate well
enough in humans to establish a self-sustaining replication cycle without a
non-human maintenance host
- Causes jaundice & hemorrhagic fever
- The virus replicates with high viremia in humans
- ~200,000 cases and ~30,000 deaths per year
- High mortality rate
- Historically up to 20%, but 5-10% is more common today
What is the initial phase of yellow fever like? What is the second phase like? Diagnosis?
- Pathology is biphasic
- Initial phase symptoms include:
- headache/fever/chills
- muscle pain
- nausea
- Symptoms that are useful for differential diagnosis include:
- head/neck flushing
- strawberry tongue
- Faget’s sign = fever + relative bradycardia
- The second phase is more serious and is associated with most mortality
- Most infections are cleared after the initial phase of the disease.
- Serious illness returns after a brief remission, with symptoms including fever, vomiting, and prostration
- Symptoms include:
- hematemesis (black vomit)
- extensive bleeding
- deepening jaundice
- renal failure/hypotension
- stupor, shock, death
• Diagnosis is through a ≥4X increase in anti-yellow fever virus antibodies in the serum or by detection of viral antigens in the serum
- Treatment includes:
- fluid replacement
• avoidance of salicylates and NSAIDs to avoid exacerbating bleeding
- antacids to decrease risk of gastric hemorrhage
- Prevention includes:
- Use the highly-effective live-attenuated YF17D vaccine
- Control mosquito infestations
- Use insect repellants to reduce the number of insect bites
Dengue fever transmission? Infectious cycle? Locations? Serotypes? Diseases?
• Dengue virus is another virus that can establish a self-sustaining infectious cycle in human
populations. It is one of the few arboviruses for which humans essentially are the virus’
maintenance host.
- Transmitted by mosquitoes
- Present in most tropical locations
- ~50 million people infected annually
- Most important arboviral cause of death
- 4 serotypes (1–4)
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- The serotypes are antigenically related but distinct
- Infection provides lifelong immunity against the same serotype
- multiple sequential infections with different serotypes is possible
- Causes 2 diseases: Classic Dengue Fever and Dengue Hemorrhagic Fever/Dengue Shock
Syndrome
What is classic dengue fever like?
- Classic Dengue Fever (also called “break-bone fever”):
- Sudden onset of flu-like symptoms, macular rash, nausea/vomiting, severe
• Patients usually recover completely after ~6-7 days
muscle/bone pain, arthralgia
What is dengue hemorrhagic fever like?
- Dengue Hemorrhagic Fever/Dengue Shock Syndrome:
- This is a biphasic disease most common in people < 15 years old
- The first phase is Classic Dengue Fever
- The second phase follows the first after a brief remission
- Symptoms include: profound prostration, circulatory collapse, dermal & mucous membrane bleeding, hemorrhagic pneumonia, thrombocytopenia
- This more severe disease course is believed to result from immune-mediated enhancement of infection: Antibodies against one serotype of Dengue Virus enhance infection by a second serotype of the virus by binding to the virus and concentrating it at the macrophages through the FC (ie, constant region on antibodies) receptor on the cells
How is the diagnosis of dengue fever made?
- Diagnosis
- Primary diagnosis is from the key symptoms of fever, hemorrhagic tendency, thromocytopenia, plasma leakage, and possible encephalitis
- Confirmation of the diagnosis is through molecular techniques such as RT-PCR for the viral genome or serological detection of antigens
- Treatment is limited to supportive care:
- Control shock due to excessive bleeding
- Ensure adequate hydration
• Antipyretics
• Avoid salicylates and NSAIDS due to bleeding risk
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• Prevention is currently limited to mosquito avoidance and control
• A dengue vaccine comprised of a yellow fever virus:dengue virus chimeric virus (“Chimerivax”) was effective against 3 of the 4 Dengue serotypes in global Phase III trials. Sanofi-Pasteur plans to market it in 2015 if regulatory approval is
received.
• Chimerivax was invented at SLU!!
What kind of a virus is chikungunya? Envelope? Replication pattern?
Togaviruses are enveloped, positive-
polarity RNA viruses with a capped,
unsegmented genome (See MHR
Topic #15 and #16 for general
information on virology). They
encode one major capsid protein, two
What is the chikungunya vector? location?
- Endemic throughout its traditional range in tropical Africa and Southern Asia
- Vector = mosquito
- The geographic area where Chikungunya is endemic is expanding very rapidly
- It is now firmly established in the Caribbean and in 2014 expanded its endemic
- Monkeys are the natural maintenance hosts
- Can establish a self-sustaining human-mosquito-human transmission cycle
due to expanding vector range secondary to climate change, plus viral evolution to replicate in more mosquito species range to southern Florida.
Chikungunya clinical features?
- Clinical features:
- Debilitating fever, nausea, vomiting, headache, and rash
- Often presents with serious arthralgia lasting from a few days to weeks
- Serious joint problems can continue for years after resolution of infection
- Recovery from infection takes longer in older patients
- Death is rare
Chikungunya diagnosis? Treatment? Prevention?
• Prevention is primarily by mosquito avoidance
- Wear bug repellent and reduce areas of stagnant water
- Screens are of limited use because the vector mosquito species are active during •
Prevention is primarily by mosquito avoidance
- Wear bug repellent and reduce areas of stagnant water
- Screens are of limited use because the vector mosquito species are active during
- Diagnosis
- IgM detection in serum or CSF
- RT-PCR
- No vaccine or antiviral therapy is available
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- Treatment is palliative
- Rest, fluids, and NSAIDs to suppress fever. Avoid aspirin.
• The US government tightly regulates Chikungunya virus as a “Select Agent” due to its potential as a bioterrorism agent. It is also is of very serious concern to the NIH and
CDC due to its pathogenicity and rapidly expanding range.
- Diagnosis
- IgM detection in serum or CSF
- RT-PCR
- No vaccine or antiviral therapy is available
the day when people are often outside
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- Treatment is palliative
- Rest, fluids, and NSAIDs to suppress fever. Avoid aspirin.
- The US government tightly regulates Chikungunya virus as a “Select Agent” due to its
potential as a bioterrorism agent. It is also is of very serious concern to the NIH and
CDC due to its pathogenicity and rapidly expanding range.
