Transcript W15-Banquet-Kramer-DINLecture - Texas Department of State

A Global Perspective on
Emerging Mosquito-Borne
Diseases
JV Irons / RR Parker Memorial Lecture
Laura D. Kramer
Wadsworth Center
New York State Dept Health
Ft. Worth, Texas
June 3, 2009
• Defined the concept of EID
• Identified factors contributing
to disease emergence
• Pointed to challenges posed
by infectious diseases
Emerging Infections: Microbial Threats to Health in the United States. Joshua Lederberg, Robert E. Shope, and
Stanley C.Oaks, Jr., Editors; Committee on Emerging Microbial Threats to Health, Institute of Medicine (1992)
“…the United States has no comprehensive
national system for detecting outbreaks of
infectious disease. Outbreaks of any disease
that is not on CDC's current list of notifiable
illnesses may go undetected or may be
detected only after an outbreak is well under
way.”
“Although many local and regional vectorcontrol programs can effectively combat
small and even medium-size outbreaks of
vector-borne disease, they are not equipped
to deal with outbreaks that are national in
scope.”
“The significance of zoonoses in the
emergence of human infections cannot be
overstated.”
Emerging Infections: Microbial Threats to Health in the United States. Joshua Lederberg, Robert E. Shope, and
Stanley C.Oaks, Jr., Editors; Committee on Emerging Microbial Threats to Health, Institute of Medicine (1992)
Outline
• Drivers of emerging / re-emerging diseases
• Re/emerging flavivirus
– West Nile
• Re/emerging alphavirus
– Chikungunya
Atlantic Monthly, 1997
Re/emerging infectious diseases
• Define the concept. EIDs are infections
•
that have newly appeared in a population,
or have existed but are rapidly increasing
in incidence or geographic range (Morse
1995)
Process
– Introduction of agent
– Establishment and dissemination
Introduction: The ‘Zoonotic Pool’
Assuming 50,000 vertebrates,
each with 20 endemic
viruses. There are likely
1,000,000 vertebrate viruses.
99.8% of vertebrate viruses
remain to be discovered
Large potential for future
zoonotic emergence!
S Morse 1993
Question
What leads to selection
or
emergence
a new agent?
Genetic and
biological factors
Physical and
environmental
factors
Vectors
Socal, political and
economic factors
Ecological
factors
Modified from Jones et al 2008 Nature 451:990.
Underlying factors in emergence:
•
Genetic and biologic factors
Microbial genetics and adaptation
Host susceptibility to infection
•
Physical environmental factor
Climate and weather
Economic development and land use
•
Ecological factors
Changing ecosystems
Human demographics and behavior
•
Social, political, and economic factors
International travel and commerce
Poverty and society inequity
War and famine
Intent to harm
Modified from King L CDC 2008
Population in millions
http://esa.un.org/unpp/
There is nowhere that is too remote to reach
Global Aviation Network
Least frequent no. passengers / day
Hufnagel et al, 2004 PNAS
Most frequent
6
Days to Circumnavigate (
the Globe
350
)
400
5
300
4
250
200
3
150
2
100
50
1
0
0
1850
1900
Year
1950
World Population in billions (
)
Speed of Global Travel in Relation to
World Population Growth
2000
Murphy and Nathanson Sems Virol 5, 87, 1994
Percentage of Population Without Reasonable Access
to Safe Drinking Water
Earth Dispatch
What is an Arbovirus?
•
•
•
•
Arthropod-borne
Group of viruses spread by arthropods
Many are zoonotic
Infection spread to incidental hosts that are not
essential to the life cycle.
Outline
• Drivers in emerging diseases
• Re/emerging flaviviruses
– West Nile
– Dengue
– Japanese encephalitis
– Yellow fever
– Kyassanur Forest
• Re/emerging alphavirus
– Chikungunya
Flavivirus: Flaviviridae (~70 members)
11 kb
WNV modified from Kuhn RJ in Kramer LD et al. Lancet Neurology 2007
Flavivirus: Flaviviridae (~70 members)
– Human pathogens
• Hemorrhagic fevers (flavi=yellow)
• Encephalitis
• Febrile illness
– 3 phylogenetic clusters
• No known vector
• Tick-borne
• Mosquito borne
– Japanese encephalitis serocomplex
» Includes JEV, SLEV, WNV
» Primarily bird viruses
» Humans not “amplifying” host
– Other serocomplexes include YFV, DENV
Japanese encephalitis serogroup
WNV
SLEV
KUNV
JEV
MVEV
Smithburn JS, Hughes TP, Burke AW, Paul JH. A neurotropic virus isolated
from the blood of a native of Uganda. Am J Trop Med Hyg. 1940;20:471–92.
Medical Department of the Uganda
Protectorate
International Health Division of The
Rockefeller Foundation.
West Nile 1994-2003
France 2000
2003
Morocco
1996
2003
1999
Bucarest
1994
Italy
1998
2000
1996
1997
2003
Tunisia
1998
2000
Israel
2003
2003
2002
Horses
Humans
Birds
Modified from the French National Reference Center for
Arboviruses, Pasteur Institute,Lyon, France
WNV geographic distribution
Pre-1999 distribution
Post-1999 distribution
West Nile Virus in North America:
Background
• Discovered in 1999 in New York
City during an outbreak of
meningitis and encephalitis in
humans and an accompanying
epizootic in birds
– Emergence during heat wave
West Nile Virus In New York - 1999
NYC - 1795
Yellow Fever Outbreak
730 Deaths
“I love the smell of malathion in the morning”
Buzz City
by
Barry Blitt
The New Yorker
Sept. 27, 2000
The Bite of Spring
by
Peter de Seve
The New Yorker
April 17, 2000
Possible pathways of introduction of WNV into the USA
• Infected Human
• Human-transported vertebrate host
– Legal
– Illegal
• Human-transported mosquito vector
• Storm-transported vertebrate host (bird)
• Intentional introduction (terrorist event)
Lanciotti et al. 1999. Origin of the
West Nile virus responsible for an
outbreak of encephalitis in the
northeastern U.S. [Science
286:2333-337.]
West Nile Virus Transmission Cycle
Mosquito vectors
Culex species
Epidemic
Secondary Hosts
Epizootic
Amplification hosts
WNV Surveillance, United States,1999-2008*:
Summary of Mosquito and Dead Bird Data
•
64 WNV-positive mosquito species reported
– Culex species account for >98% of the total reported
317 WNV-positive dead bird spp.
reported
2006: American crows and blue jay
accounted for 62% of the dead bird
reported
A Hitchcock, The Birds
* Reported as of 3/2009
Spatio-temporal Declines, American Crow
North American Breeding Bird Survey
S LaDeau; Nature. 2007. 447(7145):710-3
Equine Cases, United States,
1999-2007
16000
Total Equine: 24,681cases
Vaccine introduced
Equine Case Reports
14000
12000
10000
8000
6000
4000
2000
0
1999
2000
2001
2002
Year
2003
2004
2005
2006
2007
CDC/NCID/DVBID
WN disease
Reported incidence of West Nile virus disease by county, United States, 1999–2007
(Total cases)
(62)
(66)
(9862)
(21)
(4156)
(2539)
(1294)
2005
(1495)
2006
(1173)
2007
Hayes EB et al. EID 2006
Risk of WN disease in humans
seroprevalence studies in US (CDC)
1 of 140 infections neurologic disease
1 of 5 infections febrile illness
4 of 5 infections subclinical
Most mosquito bites not
by infected mosquito
WNV neuroinvasive disease cases in
United States (by year)
WNND Cases
Regional epidemics
2500
Avg = 1295/year
2000
1500
1000
Year
2008
2007
2006
2005
2004
2003
2002
2001
0
2000
500
1999
No. NID cases
3000
WNV neuroinvasive disease cases and deaths
100%
3000
80%
2500
2000
60%
1500
40%
1000
20%
500
0
0%
1999
2000
2001
2002
2003
NID cases
2004
2005
mortality
2006
2007
% mortality
No. of NID cases
3500
Reported WNND Cases and WNV Deaths in
Humans,
United States, 1999-2008*
Year
Encephalitis/
NonMeningitis
11,820Encephalitis/
WNND CasesTotal
AFP
(includes some Meningitis AFP
AFP) x 140 infections/WNND
19992002
3,088
2003
2,866
--
--
Total
WNND
Deaths
3,088
303
2,866
264
~ 1.65 Million Infections
--
--
WNV
Widespread
and
Pervasive
2004
1,142
6
33
1,148
2005
1,294 in Environment
15
82
1,309
2006
2007
2008
Total
1,459
36
101
1,495
Produced
Widespread
and
1,217
10
63
1,227
665 Pervasive
1 Impact
21
687
11,616
* Reported as of 11/04/2008
68
300
11,820
100
119
177
124
44
1,114
West Nile virus neuroinvasive disease
cases by age group and gender, 19992006*
Incidence per 100,000
25
Male
Incidence
20
Female
Incidence
15
10
5
0
0-9
10-19
20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
Age Group (yr)
* Reported as of 5/2/2007
Sejvar J CDC
Proportion with WNF
Proportion of viremic blood donors
developing West Nile fever
Colorado, 2003
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
18-29
30-39
40-49
50-59
Age Group
Vector Borne Zoonotic Dis 2007;7:479
60-69
70-79
Risk factors for neuroinvasive disease
• Strong evidence
– Age
 Risk increases ~1.5 times per decade
– Organ transplant recipients
 ~40% develop neuroinvasive disease (>40 times the
risk as population-at-large)*
– Hematological malignancies
 Experimental infection and individual case reports
(risk remains undefined)
* Kumar et al. Am J Transplant 2004;4:1883-8
Risk factors for neuroinvasive disease
• Weaker evidence
– Diabetes
– Hypertension
– Alcohol abuse
– Chronic renal disease
– Cardiovascular disease
The West Nile Virus “Iceberg” - 2
Acute WNV
WNV long term effects
Sejvar CDC
Temporal profile of recovery—
WNV “Poliomyelitis”
100
Baseline Strength
80
Level of recovery (18)
60
40
20
0
Sejvar J CDC
Novel modes of virus transmission
•
Transfused blood
– Blood supply screening began in 2003
– More than 1000 viremic blood donors identified 2003
- 2004
• Transplanted organs
• Breast milk
Greatest
risk – exposure to mosquito bite !!
– One case, infant asymptomatic
• Transplacental transmission
– Single case 2002 with severe outcome to infant
• Percutaneous, occupational exposure
• Dialysis?
•
•
•
•
•
•
Conclusions 1 – North America
Rapid spread across USA (<4 years to Pacific
Coast)
• Bird migration and random bird movements
Many possible important avian hosts and competent
mosquito vectors (unprecedented infection
prevalence)
Significant impact on wildlife and domestic animals.
Persistent seasonal outbreaks. Incidence varies
regionally.
High infection incidence in humans has led to
unusual modes of transmission.
Age and immunosuppression highly significant risk
factors for neuroinvasive disease. Role of other risk
factors unclear, but possibly important.
West Nile Virus in Latin America
2002 –
2004
2006
Little evidence of human and
animal disease in Latin America
• Less virulent virus circulating?
• Poor surveillance?
• Serological cross reactivity with other
flaviviruses?
• Previous exposure to other circulating
flaviviruses modulating disease expression?
• Other causes?
West Nile Virus
Puerto Rico, 2007
•
•
•
•
•
•
Sentinel chicken surveillance: up to 50% chickens
seroconverted per week for over two months
3 viremic human blood donors
7 sick horses; 1 death
Active human surveillance: only one human with West
Nile fever; no neuroinvasive disease
WNV isolated from chickens and Culex mosquitoes
Strain identical to that circulating in United States
Future issues
West Nile virus is endemic in the western hemisphere
• Vaccines successful for
•
•
•
equines but need to weigh cost
effectiveness for humans
Therapeutics / antivirals
Long term sequelae
Control and risk prediction
Pools at foreclosed homes raise West Nile threat in Dallas County
10:38 PM CDT on Friday, May 22, 2009
By THEODORE KIM / The Dallas Morning News
[email protected]
braceforimpactnow.blogspot.com
Outline
• Drivers of emerging diseases
• Re/emerging flavivirus
– West Nile
• Re/emerging alphavirus
– Chikungunya
Atlantic Monthly, 1997
Togaviridae: Alphaviruses
Genome:
Single stranded, positive sense RNA
5’ capped , 3’ polyadenylated
Cytoplasmic replication
Structural proeins encoded at 3’ end in subgenomic message
Insect transmitted
3 disease patterns:
Arthropathy (Sindbis, Ross River, Chikungunya)
Systemic febrile illness (Semliki forest, VEE)
Encephalitis (EEE, WEE, VEE)
Chikungunya
In Swahili, “chikungunya” : “ that which contorts
or bends “up”
Disease:
High fever (103-104 F)
Rash
Severe incapacitating arthritis/arthralgia
– Generalized
– Usually acute
Hemorrhagic manifestations have been reported
Rarely fatal
G. Pialoux et al., 2007, Lancet Infect Dis
A.M. Powers and C.H. Logue, 2007 J Gen Virol,
CHIKV Transmission Cycle
forested areas in West & Central Africa
Forest Aedes spp.
eg. Forest redtail monkey
Ae africanus
Ae luteocephalus
Ae furcifer-taylori
Modified from Gould EA and Higgs S 2009 Trans Royal Soc Trop Med Hyg
CHIKV Transmission Cycle
urban in Asia
Aedes aegypti
& Ae. albopictus
Powers AM, Logue CH J Gen Virol. 2007 88:2363.
Recent outbreaks of Chikungunya
2004-2007
266,000 cases
Enserink, M. (2007) Science 318: 1860-1861
Chikungunya Virus Outbreak
878 imported cases to France
Pialoux et. al 2007 Lancet Inf Dis, 7:319-327
Recent outbreaks of Chikungunya
2004-2007
>1.4 million cases
Enserink, M. (2007) Science 318: 1860-1861
Recent outbreaks of Chikungunya
2004-2007
New emergence in
2007: >200 cases
Enserink, M. (2007) Science 318: 1860-1861
Mosquito species were different in
various outbreaks
Ae. aegypti
Ae. albopictus
Enserink, M. (2007) Science 318: 1860-1861
Re-emergence in the 2000s
Domestic epidemic cycles
Ae albopictus on islands and Italy
Ae. aegypti in India
Mosquito-borne virus hits 20,000
HEALTH MINISTRY ISSUES ALERT OVER CHIKUNGUNYA DISEASE
By: APIRADEE TREERUTKUARKUL
Bangkok Post 05/24/09
Charrel et al. 2007. N Engl J Med 356;8
Presence of Aedes albopictus in Europe, 2007
ECDC/WHO Mission report Sept 2007
Expansion of world distribution of
Aedes albopictus
Charrel et al. 2007. N Engl J Med 356;8
Factors involved in re-emergence of
Chikungunya virus
•
•
•
•
Biologic and genetic
– Non-immune population
–
Adaptation of virus to new mosquito: Ae. albopictus
Ecologic conditions
–
–
–
Standing water due to droughts
Warm European summer
Mosquito abundance
Social, economic, political
–
–
–
International travel
Previous introduction of Ae. albopictus into Reunion Island & Italy
Delayed identification and control of initial outbreaks
Physical environment
– Stored water/atificial breeding sites
Modified from Chretien JP, Linthicum KJ. Lancet. 2007
Can Chikungunya virus emerge in US?
•
•
37 imported cases in 2005-2006
 No autochthonous transmission so far
Components of the transmission cycle?
 Climate in southern states 
 Humans 
 Monkeys X
 Mosquitoes ????
Distribution of Ae. aegypti
in Americas
1970 – after mosquito
eradication
2002
www.cdc.gov/ncidod/dvbid/dengue/map-ae-aegypti-distribution.htm
Distribution of Ae. albopictus
in US, year 2000
http://www.cdc.gov/ncidod/dvbid/Arbor/albopic_97_sm.htm
Can Chikungunya virus emerge in US?
•
•
•
37 imported cases in 2005-2006
Components of the transmission cycle?
 Climate in southern states 
 Humans 
 Monkeys X
 Mosquitoes 
Human behavior ???
Can we predict the next new emerging zoonosis?
“In general, there is no way to predict
when or where the next important new
zoonotic pathogen will emerge or what
its ultimate importance might be.”
F.A. Murphy, ICEID 1998
Emerg. Infect. Dis. 1998 4: 429-435
Malaria, yellow fever, dengue, West Nile virus, chikungunya,
WHAT’S NEXT?
Thank you!
QUESTIONS???????