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The Threats of Rift Valley Fever and Chikungunya

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Title: The Threats of Rift Valley Fever and Chikungunya


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

2
Rift Valley Fever Virus
Chikungunya
Epizootic Cycle Large Scale
Animal Disease Associated Human
infection
Urban Epidemic Cycle Large Scale Human
Epidemics Dengue Yellow Fever Onyong-nyong Ro
ss River virus
3
Rift Valley fever virus
  • Floodwater Aedes sp
  • The Basics
  • FamilyBunyaviridae, genus Plebovirus
  • Zoonotic pathogen
  • Humans
  • Hemorrhagic fever
  • Encephaltis
  • Retinitis
  • Livestock
  • Transmission/Maintenance
  • Mosquito
  • Known Vectors
  • Floodwater Aedes Sp.
  • Vertical Transmission
  • Culex (Amplified virus)
  • Potential Vectors
  • North American mosquitoes
  • Sand flies
  • Mucosal

Culix Aedes Others
Floodwater Aedes sp.
4
RVFV Disease
  • Livestock Disease
  • Abortion storms (sheep, cattle, goats).
  • High mortality in young animals
  • High Priority Pathogen for USDA
  • Human Disease
  • Flu like symptoms (majority of cases)
  • Hemorrhagic or encephalitic forms (1)
  • Hemorrhagic form has hepatic involvement
  • 20-30 case fatality rate in recent outbreaks
  • Retinitis

5
Is RVFV a Threat to the United States?
Current Distribution of Rift Valley Fever
Virus Outbreaks of Note Isolated in
Kenya (1930) - Sporadic outbreaks at
3-10 yrs. Egypt 1977-78 -
18,000 human cases, 600 deaths East
African Epizootic (1997) - 89,000 human
cases - 500 human deaths
Saudi Arabia/Yemen (2000) -1st
documented outbreak outside of
Africa/Madagascar -13.9 mortality
among hospitalized
http//www.cdc.gov/ncidod/dvrd/spb/mnpages/dispage
s/rvf/rvfmap.htm
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
  • Human Disease
  • 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
  • Intentional
  • Accidental
  • Importation of infected mosquitoes
  • Importation of infected livestock/materials
  • Vector Competence?
  • Multiple mosquito species can transmit
    experimentally
  • North American Culex and Aedes Species
  • Maintenance and Spread
  • Livestock industry
  • 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.)
  • Worldwide
  • Therapeutics
  • Ribavirin
  • Interferon
  • Vaccines
  • Livestock
  • 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
  • Humans
  • Inactivated vaccine is effective, but requires
    multiple boosts
  • Live attenuated vaccines (MP-12)
  • Others?
  • Biological Questions
  • Vector potential and transmission

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 132-164)
  • 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
  • FamilyTogaviridae, genus Alphavirus (Semliki
    Forest virus Complex)
  • Human Disease
  • Rural cycle
  • Ae. Africanus and Ae. Furcifer maintenance with
    wild primates
  • Urban cycle
  • Ae. Aegypti
  • Ae. Albopictus
  • Related viruses
  • Onyong-nyong
  • 1959 African epidemic gt2 million cases
  • Re-emerged in 1996
  • Anopheles mosquitoes
  • Ross River virus
  • Australian
  • 1979 epidemic in South Pacific

Ae. Aegypti, Ae. albopictus
Ae. Aegypti, Ae. albopictus
Urban Cycle
12
Chikungunya
  • Human Disease
  • Chikungunya (Swahili) That which bends up.
  • Severe arthritis/arthralgia/myalgia
  • High fever (103-104 F)
  • Rash
  • Hemorrhagic manifestations have been reported
  • Severe incapacitating arthritis/arthralgia.
  • Generalized
  • 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 13 to 150 for CHIK and related viruses
  • Reunion Island 13 or population had clinically
    apparent disease (approximately 250,000 cases).
  • Infected individuals develop a high titer viremia

13
Is Chikungunya a Threat to the United States?
Chikungunya Distribribution 1952-2006
http//www.cdc.gov/ncidod/dvbid/Chikungunya/index.
htm
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
  • Endemic Chikungunya
  • Congo 2004 (re-emergence after 39 years)
  • Malaysia 2007 (re-emergence after 7 years)
  • Parola et al., Emerg Infect Dis 2006
    1213931399.
  • Schuffenecker, et al., PLoS Med 2006 3e263.

15
Threat of CHIK Introduction
  • Sporadic outbreaks
  • Returning Travelers
  • 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
  • Vaccines
  • Experimental Live attenuated vaccine
  • Therapeutics
  • Non-steroidal anti-inflammatory drugs
  • Basic Biology
  • 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
  • Viral factors
  • Host factors
  • Macrophages
  • 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
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