Arboviruses Flashcards
What is an arbovirus?
Viruses maintained in nature in cycles involving hematophagous arthropod vectors and susceptible vertebrate hosts
What kinds of nucleic acid do most arboviruses have?
nearly all have RNA genomes
Arthropod vectors
Primarily mosquitoes, but also ticks, biting flies
Infected vectors transmit virus to vertebrate hosts during feeding
Two types of vertebrate hosts for arboviruses
- Those that serve as main sources of infections for vectors (reservoirs): may or may not develop disease
- Those that don’t serve as reservoirs, but in which disease may occur (humans for most of these)
Has to do with how high titer the serum viremia is (if high enough, can be a reservoir)
What are the exceptions to humans being a dead-end host of virus?
Dengue virus
Yellow Fever virus
Zika virus
Some alphaviruses:
Ross River virus
Chikungunya virus
Venezuelan equine encephalitis virus
Role of Mosquito in Arbovirus Transmission
- Female mosquito ingests blood from viremic vertebrate.
- Virus replication in the mosquito midgut.
- Systemic spread in mosquito.
- Virus replicates and accumulates in salivary glands.
- Mosquito injects saliva/virus into skin during next blood meal.
After biting an infected vertebrate host, is a mosquito immediately infectious for humans?
No, because virus has to replicate in mosquito first
Extrinsic incubation period
Arboviruses: Major outcomes of human infection
In order of how common:
- Asymptomatic
- Febrile illness
- Neurologic disease: encephalitis, meningitis
- Arthritis/MSK disease signs
- Hemorrhagic fever
What are the three taxonomic families that contain most of the arboviruses of public health importance?
Bunyaviridae
Flaviviridae
Togaviridae
Major global arboviruses
Dengue viruses (DENV) West Nile virus (WNV) Zika virus (ZIKV) Chikungunya virus (CHIKV) Yellow Fever virus (YFV) Japanese encephalitis virus (JEV)
Major arboviruses found in the United States
West Nile virus (WNV) St. Louis encephalitis virus (SLEV) La Crosse virus Eastern equine encephalitis virus Colorado Tick Fever virus
Dengue virus sypmtoms
75% asymptomatic
Cause two syndromes:
1. Dengue Fever (DF) 24%
• An acute febrile illness characterized by headache, muscle and joint pain, and rash.
- Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) 1%
• Characterized by thrombocytopenia, capillary leakage, damage to liver
• Fluid loss in tissue spaces can lead to hypovolemic shock and death (DSS)
What percent of the world population is a risk of dengue viruses?
50%!
Factors contributing to re-emergence of dengue viruses and DHF
Cocirculation of all 4 serotypes Global pop growth Increased air travel Unplanned, uncontrolled urbanization Lack of effective mosquito control
Dengue virus characteristics
4 serotypes (1-4)
Members of the Flavivirus genus of the Flaviviridae
Mosquito-borne
• Aedes aegypti
• Aedes albopictus
Transmission of dengue viruses
Maintained in human-mosquito-human transmission cycle
Risk factors for development of DHF/DSS following dengue virus infection
- A second dengue infection by a different serotype
- Age (under age 15)
- Host genetic background
- Viral genotype
- Each of the 4 DENV serotypes is composed of several genotypes
Disease severity is determined by a combination of host and viral factors: Pre-existing immunity and virus genetics are critical determinants
Antibody-dependent enhancement (ADE) of disease severity Hypothesis
Ab response to 1st infection protects against a 2nd infection from that serotype
But those Ab can cross-react with other serotypes at first but over time lose their cross-reactive Ab
2nd infection with a different serotype: cross-reactive Ab are subneutralizing. They mediate enhanced infection of specific cells via FcγRs.
Leads to increased viral replication and immune activation (increased cytokines etc.)
Chikungunya virus
Reemergence of mosquito-transmitted alphavirus
Can cause chronic MSK disease
Acute stage: fever, severe pain in joints
For many, that pain can last for months to years
No specific treatments, just for symptoms
Zika virus
Flavivirus transmitted by Aedes species of mosquitoes
Prior to 2007, only 14 documented cases of human Zika virus disease
Similar to CHIKV, ZIKV has spread dramatically in the last 5-8 years
Infection: asymptomatic (80%) to fever, muscle/joint pain, conjuctivitis (20%)
Microcephaly in newborns?
Yellow fever and dengue fever in the US
Historically caused infection, but not really today because of socioeconomic factors (air conditioning, higher per capita income)
West Nile Virus
Encephalitic flavivirus
Encephalitis
Maintained in an enzootic cycle involving mosquitoes and birds
Humans are a dead-end host
Seasonal (end of summer)
Treatment is supportive
Arbovirus disease burden in US
Pretty low
West Nile is most common in US
Symptoms of west nile virus disease
Majority (~80%) are asymptomatic
WNV Fever (~20%) • Abrupt onset of fever, headache, fatigue
WNV neuroinvasive disease ( less than 1%)
• Fever, headache, altered mental status, neck stiffness
• Typically manifests as encephalitis (63%), meningitis (33%), or acute flaccid paralysis (3%)
• Most cases occur in elderly people and those with impaired immune systems
• Long term neurological sequelae are common
West Nile Virus pathogenesis
Virus replicates locally at site of inoculation (Keratinocytes,
dendritic cells)
Infected cells migrate, spread virus to lymph nodes
Seeds primary viremia
Virus gains access to the CNS
Mechanism by which WNV invades CNS is unclear
WNV directly infects neurons
Neuronal injury in brain stem, hippocampus, cortex,
cerebellum, spinal cord
Non-mosquito transmission of WNV
Solid organ transplantation and blood transfusion
What do Dengue viruses and Yellow Fever virus cause
Hemorrhagic fever
What do Japanese encephalitis virus and West Nile virus cause
Encephalitis
What does Chikungunya virus cause
Acute and chronic arthritis
