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1. The Threats of Rift Valley Fever and Chikungunya Mark T. Heise
The Dept. of Genetic
The Carolina Vaccine Institute
The University of North Carolina
3. Rift Valley fever virus Floodwater Aedes sp The Basics
Family:Bunyaviridae, genus: Plebovirus
Floodwater Aedes Sp.
Culex (Amplified virus)
North American mosquitoes
4. RVFV Disease Livestock Disease
Abortion storms (sheep, cattle, goats).
High mortality in young animals
High Priority Pathogen for USDA
Flu like symptoms (majority of cases)
Hemorrhagic or encephalitic forms (1%)
Hemorrhagic form has hepatic involvement
20-30% case fatality rate in recent outbreaks
6. Potential Impact of RVFV in U.S. Livestock industry
Direct Loss due to virus induced disease
Loss of Export Market
Outbreak would cause OIE imposed ban on exports for at least 6 months, and up to 4 years if RVFV is considered endemic.
$7.3 billion in beef exports in 2003
Paralysis of Transportation System
Livestock handlers most at risk
Vector borne exposure
Mucosal transmission from infected animals
Healthcare workers (diagnostic laboratories)
General public (Limited direct risk, Panic)
7. Is RVFV a Threat to the United States? Significant Emerging Pathogen
OIE List A pathogen
USDA/CDC overlap agent
#3 agent on Animal Biological Threat Agents and Research Priority list.
Several means of potential introduction
Importation of infected mosquitoes
Importation of infected livestock/materials
Multiple mosquito species can transmit experimentally
North American Culex and Aedes Species
Maintenance and Spread
Potential for vertical transmission
Susceptibility of North American Wildlife?
8. RVFV: Ongoing Questions/Needs? Surveillance
United States (Limited resources for animal testing in U.S.)
Existing live attenuated vaccines show promise
Elicit long term immunity
Generally safe, though contraindicated for pregnant animals
Not recommended for non-endemic areas
New vaccine alternatives
Inactivated vaccine is effective, but requires multiple boosts
Live attenuated vaccines (MP-12)
Vector potential and transmission
Can U.S. Mosquito species efficiently transmit?
Can U.S. Mosquito species vertically transmit virus?
Susceptibility of North American Wildlife
9. Developing Improved RVFV Vaccines and Diagnostic Agents Develop improved RVFV vaccines for human and livestock use
Goals: Safe vaccines that elicit long-lived RVFV immunity, with minimal boost requirements, DIVA compatible (Heise, Ross, and Burt Labs).
Alphavirus Replicon-based RVFV vaccines
Elicit protective immunity against peripheral and mucosal RVFV challenge in mouse models
Elicit protective immunity in vaccinated sheep (Neut titers of 1:32-1:64)
DNA vaccines with RVFV Gn protein linked to C3d molecular adjuvant
Elicit RVFV specific antibody responses in immunized mice
Can be modified for livestock use
RVFV virus like particles (VLPs)
RVFV Diagnostic Assays (Doms, Burt, and Heise Labs)
Goals: Develop non-virus based immunology reagents
Experimental RVFV cell fusion and pseudotyping assays developed
Virus free RVFV specific neutralization test developed and validated against a standard virus-based RVFV neutralization assay.
10. Summary I: RVFV Potential for significant impact on livestock industry/economy
Epizootic would have significant human health impact (potentially more severe than WNV).
Endemic potential in Western Hemisphere?
Need for improved diagnostics, vaccines, and antivirals.
11. Chikungunya The Basics:
Family:Togaviridae, genus: Alphavirus (Semliki Forest virus Complex)
Ae. Africanus and Ae. Furcifer maintenance with wild primates
1959 African epidemic >2 million cases
Re-emerged in 1996
Ross River virus
1979 epidemic in South Pacific
12. Chikungunya Human Disease
Chikungunya (Swahili): That which bends up.
High fever (103-104 F)
Hemorrhagic manifestations have been reported
Severe incapacitating arthritis/arthralgia.
Usually acute (Several days to several weeks, though 20% of individuals have long-term joint complaints)
Rarely if ever fatal
Apparent-to-inapparent infection ratio varies from 1:3 to 1:50 for CHIK and related viruses
Reunion Island: 1:3 or population had clinically apparent disease (approximately 250,000 cases).
Infected individuals develop a high titer viremia
14. Are Chikungunya or Related viruses Threats to the United States? Epidemic Chikungunya (2005-2007)
Groups within Central/East African CHIK strains*
Reunion Island 266,000 cases
Approximately 1/3 of population
Presumed vector is Aedes albopictus
India 1.4 million cases
Presumed vector is Aedes aegypti
Emergence in new regions due to infected travelers a concern
United States: 37 imported cases 2005-2006
Competent vectors present
No evidence for transmission
Congo: 2004 (re-emergence after 39 years)
Malaysia: 2007 (re-emergence after 7 years)
Parola et al., Emerg Infect Dis 2006 12:1393–1399.
Schuffenecker, et al., PLoS Med 2006; 3:e263.
15. Threat of CHIK Introduction Sporadic outbreaks
Potential for localized spread
Large Scale Epidemic?
Risk in areas with competent mosquito vectors
Possibility of endemic status?
Dengue and YFV as examples
16. What do we need? Surveillance
Experimental Live attenuated vaccine
Non-steroidal anti-inflammatory drugs
Viral vector biology
Basic pathogenesis of virus induced disease
17. Basic Biology of CHIK and Related Viruses Vector Biology
Epidemic on Reunion involved Ae. Albopictus
Genetic changes in virus?
Other potential vectors?
Pathogenesis of virus induced-arthritis
Complement activation (RRV)
18. Summary II: Chikungunya Potential for large scale epidemics with significant human morbidity
Experience with other viruses that use similar mosquito vectors suggests that large scale outbreaks in U.S. may not occur
Need for improved therapeutics and vaccines
19. References RVFV Chikungunya