A global perspective on emerging mosquito borne diseases
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A Global Perspective on Emerging Mosquito-Borne Diseases. Laura D. Kramer Wadsworth Center New York State Dept Health. JV Irons / RR Parker Memorial Lecture. Ft. Worth, Texas June 3, 2009. Defined the concept of EID Identified factors contributing to disease emergence

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A Global Perspective on Emerging Mosquito-Borne Diseases

Laura D. Kramer

Wadsworth Center

New York State Dept Health

JV Irons / RR Parker Memorial Lecture

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 vector-control 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)


Atlantic Monthly, 1997

Outline

  • Drivers of emerging / re-emerging diseases

  • Re/emerging flavivirus

    • West Nile

  • Re/emerging alphavirus

    • Chikungunya


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

Ecological

factors

Socal, political and

economic 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

Most frequent

Least frequent no. passengers / day

Hufnagel et al, 2004 PNAS


400

)

)

350

5

(

300

(

e

t

a

s

4

250

g

n

i

v

o

e

a

i

l

b

l

n

i

o

200

b

l

m

3

G

u

n

i

c

e

r

150

n

i

h

C

t

o

2

i

t

o

a

t

100

l

u

s

y

p

a

o

1

50

P

D

d

l

r

0

o

0

W

2000

1850

1900

1950

Year

Speed of Global Travel in Relation to

World Population Growth

6

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

1999

Morocco

Bucarest

1996

2003

2000

1994

Italy

1998

1996

1997 2003

1998

2000

Tunisia

2003

Israel

2003

2002

Modified from the French National Reference Center for Arboviruses, Pasteur Institute,Lyon, France

Horses

Humans

Birds


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

  • 64WNV-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 jays

    • accounted for 62% of the dead birds

    • 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


16000

14000

12000

10000

8000

6000

4000

2000

0

1999

2000

2001

2002

2003

2004

2005

2006

2007

Equine Cases, United States, 1999-2007

Total Equine: 24,681cases

Vaccine introduced

Equine Case Reports

Year

CDC/NCID/DVBID


WN disease


(1294)

2005

(1495)

2006

(1173)

2007

Reported incidence of West Nile virus disease by county, United States, 1999–2007

(Total cases)

(21)

(62)

(66)

(4156)

(9862)

(2539)

Hayes EB et al. EID 2006


Risk of WN disease in humansseroprevalence 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


Regional epidemics

Avg = 1295/year

WNV neuroinvasive disease cases in United States (by year)

No. NID cases

Year


WNV neuroinvasive disease cases and deaths

No. of NID cases

% mortality


11,820 WNND Cases

x 140 infections/WNND

~ 1.65 Million Infections

Reported WNND Cases and WNV Deaths in Humans,United States, 1999-2008*

WNV Widespread and Pervasive in Environment

Produced Widespread and Pervasive Impact

* Reported as of 11/04/2008


West Nile virus neuroinvasive disease cases by age group and gender, 1999-2006*

25

Male

Incidence

20

Female

Incidence

15

Incidence per 100,000

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


0.8

0.7

0.6

0.5

0.4

Proportion with WNF

0.3

0.2

0.1

0

18-29

30-39

40-49

50-59

60-69

70-79

Age Group

Proportion of viremic blood donorsdeveloping West Nile feverColorado, 2003

Vector Borne Zoonotic Dis 2007;7:479


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”

BaselineStrength

100

80

Level of recovery (18)

60

40

20

0

Sejvar J CDC


Greatest risk – exposure to mosquito bite !!

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

    • 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 [email protected]

braceforimpactnow.blogspot.com


Atlantic Monthly, 1997

Outline

  • Drivers of emerging diseases

  • Re/emerging flavivirus

    • West Nile

  • Re/emerging alphavirus

    • Chikungunya


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 Cycleforested areas in West & Central Africa

Forest Aedes spp.

Ae africanus

Ae luteocephalus

Ae furcifer-taylori

eg. Forest redtail monkey

Modified from Gould EA and Higgs S 2009 Trans Royal Soc Trop Med Hyg


CHIKV Transmission Cycleurban in Asia

Aedes aegypti

& Ae. albopictus


Powers AM, Logue CH J Gen Virol. 2007 88:2363.


266,000 cases

Recent outbreaks of Chikungunya 2004-2007

Enserink, M. (2007) Science 318: 1860-1861


Chikungunya Virus Outbreak878 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


Ae. albopictus

Mosquito species were different in various outbreaks

Ae. aegypti

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 20,000HEALTH 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. aegyptiin Americas

1970 – after mosquito eradication

2002

www.cdc.gov/ncidod/dvbid/dengue/map-ae-aegypti-distribution.htm


Distribution of Ae. albopictusin 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???????


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