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Emerging Arboviruses Laura D. Kramer Wadsworth Center New York State Dept Health and State University of New York at Albany [email protected] ASM Northeast regional meeting 20-21 October 2015 Atlantic Monthly, 1997

Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

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Page 1: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Emerging Arboviruses

Laura D. Kramer

Wadsworth Center

New York State Dept Health

and

State University of New York at Albany

[email protected]

ASM Northeast regional meeting 20-21 October 2015

Atlantic Monthly, 1997

Page 2: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Background and concepts

Reasons for epidemic

transmission and spread

Emerging mosquito-borne viruses

• West Nile virus

• Dengue virus

• Chikungunya virus

Risk in US

Why have we seen such a dramatic

increase in epidemic activity and

geographic spread of vector-borne

diseases?

Page 3: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

BF - Barmah Forest MAY - Mayaro VEE - Venezuelan Equine Encephalitis CE - California Encephalitis MVE - Murray Valley Encephalitis WEE - Western Equine Encephalitis Chik - Chikungunya ONN – O’nyong-nyong WN - West Nile CCHF - Congo-Crimean Hemorrhagic Fever ORO - Oropouche WSL - Wesselsbron DEN - Dengue RVF - Rift Valley Fever YF - Yellow Fever

ZIK- Zika EEE - Eastern Equine Encephalitis RR - Ross River JE - Japanese Encephalitis SLE - St. Louis Encephalitis KFD - Kyasanur Forest Disease SIN - Sinbis LAC - LaCrosse Encephalitis TBE- Tick-Borne Encephalitis

DEN DEN DEN

DEN

DEN DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

DEN

JE

JE

JE

JE JE

JE

CHIK CHIK

CHIK

CCHF

CCHF

CCHF

CCHF

MVE

RR

BF

SIN SIN

TBE

TBE

CE

WN

WN WN

WN

WN

WN

WN

WN

WN

WN

WSL

ONN

RVF

RVF

RVF

KFD

YF YF

YF YF

YF ORO

ORO

ORO MaY VEE

VEE

VEE

EEE

LAC SLE

Global Emergence of Epidemic Arboviral Diseases

WN

WN WN

EEE SLE

WN

WN WN

DEN

DEN

DEN

DEN

DEN

DEN

POW

YF

JE

DEN

DEN

RVF

WNV

Zik

RVF

Arthropod-borne (arbo) viruses:

• Almost exclusively RNA viruses

• >120 associated with human

disease

• Most impt families Flaviviridae,

Togaviridae, or Bunyaviridae

• Significant global expansion in

recent decades

Page 5: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue
Page 6: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

1950 1985 2000 2030

Bill

ion

s o

f P

eo

ple

Estimated Number of People Living in Urban Areas

Source: UN

Page 7: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Urbanization The Case of Dhaka, Bangladesh

1,500,000

14,000,000

0

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

14,000,000

16,000,000

1970 2008

Num

ber

of

people

Source: UN

Page 8: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Mosquitoes that have travelled the world...

…and spread many viruses to humans

Aedes aegypti

DENV, YFV, CHIK, etc.

Aedes albopictus

DENV, CHIK, etc.

Culex pipiens

WNV, SLEV, etc.

Page 9: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

0

100

200

300

400

500

600

700

1950s 1960s 1970s 1980s 1990s 2000s

mil

lio

ns

of

Pa

ssen

ger

s

Mean Annual Number of Airline Passengers by Decade,

United States, 1954-2007

Source: RITA, DOT

Page 10: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Civil Aviation Traffic

Least frequent no. passengers / day Most frequent Hufnagel et al, 2004 PNAS

There is nowhere that is too remote to reach

Page 11: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Speed of Global Travel in Relation to

World Population Growth

W o r l

d P

o p u

l a t i o

n i

n b

i l l i o

n s

(

)

D a y s

t o C

i r c u

m n

a v i g

a t e

(

)

t h

e G

l o b e

Year 1850

0

400

350

300

250

200

150

100

50

2000

0

1900 1950

1

2

3

4

5

6

Murphy and Nathanson Sems Virol 5, 87, 1994

Page 12: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Background and concepts

Reasons for epidemic

transmission and spread

Emerging mosquito-borne viruses

• West Nile virus

• Dengue virus

• Chikungunya virus

Risk in US

Why have we seen such a dramatic

increase in epidemic activity and

geographic spread of vector-borne

diseases?

Page 13: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Ciota and Kramer et al., 2013

West Nile virus- a case study for

geographical expansion

Page 14: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

3 5

West Nile virus (Flavivirus; Flaviviridae)

Modified from Kuhn RJ in Kramer LD et al. Lancet Neurology 6:171

Page 15: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

West Nile Virus Transmission Cycle

Mosquito vectors Culex species

Amplification hosts Epizootic

Secondary Hosts

Page 16: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Host competence: the vertebrate host

Spinal cord titers

0

2

4

6

8

10

0 2 4 6 8 10 12

Time post-inoculation (days)

Avg

Lo

g 1

0 vi

rus

titer

(PF

U/m

l)

Pigeon Sparrow Crow LOD CNS

Bernard KA et al. 2002

0%

mortality

LD50>105

20% mortality

LD50>105 100%

mortality

LD50<101

Blood titers

0

2

4

6

8

10

0 2 4 6 8 10 12

Time post-inoculation (days)

Avg

Log

10

viru

s tit

er (P

FU/m

l or g

)

Pigeon Sparrow Crow LOD blood

Corvus brachyrhynchos Passer domesticus Columba livia

Page 17: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Snappin et al., 2007, JVirol

West Nile virus strain displacement

WN02

NY99

Year of isolation

Pe

rce

nt

of

str

ain

s

0

20

40

60

80

100

1999 2000 2001 2002 2003 2004 2005 – 2011……

E – V159A

Pe

rce

nt

tra

ns

mis

sio

n

NY99

WN02

5 7 9 14 0

10

20

30

Days post-feeding

ND

Cx. pipiens

NY99

WN02

5 7 9 14 0

10

20

30

Days post-feeding

Cx. tarsalis

*

*

* *

Ebel et al., 2004, AJTMH; Moudy et al., 2007,

AJTMH

5 7 9 14 0

10

20

30

40

NY99-2094 NY99-3557 WN02-1986 WN02-1956

Days post-feeding

Cx. quinquefasciatus

Page 18: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

0

0.2

0.4

0.6

0.8

1

0 100 200 300 400 500

Degree Days (C)

Fra

cti

on

Tra

nsm

itti

ng

NY99

WN02

5d

10d

1d

15d32C

12C

Kilpatrick et al., 2008. PLoS Pathog. 4(6)

Transmission accelerates with increasing

temperature , tT4 (fitted model)*

* Integrating viral genotype, time, temperature

Page 19: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Importance of socioeconomic conditions and land use

braceforimpactnow.blogspot.com

ENVIRONMENTAL FACTORS

Pools at foreclosed homes raise West Nile

threat in Dallas County

By THEODORE KIM / The Dallas Morning

News

May 22, 2009

[email protected]

Page 20: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Dengue

Page 21: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Dengue

• Worldwide Impact

– Currently > 2.5B at risk

– 50-100M cases DEN fever

per year

– 250,000 – 500,000 cases of DHF

• Virus Classification

– Flaviviridae, Flavivirus

– Single-stranded, + sense, RNA

genome

– Enveloped virus

Mature dengue virus viewed through

cryo-electron micro-scopy

Page 22: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Dengue Virus

• 4 genetically distinct

serotypes

– Lifetime homologous (within

serotype) immunity

– Short-term heterologous

(between serotype) cross-

protection

• Significant variation within

serotypes (strains)

Figure. Partial phylogeny of flaviviruses

Page 23: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

50-90%

• Dengue fever (breakbone fever)

– Fever, retro-orbital headache, muscle

and joint pain, nausea/vomiting, rash

• DHF/DSS (~ 0.5-10%)-often

associated with 2ndary infection with

heterologous serotype

– Fever

– Hemorrhagic manifestations

– Leaky capillaries

– Low platelet count

– DSS = DHF + signs of circulatory

failure

• 2009 WHO classification:

Den without warning

Den with warning

Severe DEN

Dengue disease Severe DEN

Page 24: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Transmission Cycle

Rural cycle: Ae. albopictus

Ae. polynesiensis

Ae africanus

Ae luteocephalus

Ae furcifer-taylori

Page 25: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

DHF in the Americas (1980 – 2007)

02,000

4,0006,000

8,00010,000

12,00014,000

16,00018,000

20,000

Rep

ort

ed

Cases

1980 1985 1990 1995 2000 2005

Year

* Data: PAHO (Nov. 30, 2007)

Page 27: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Chikungunya Virus

and Disease

First isolated in Tanzania 1952

Family - Togaviridae, Genus – Alphavirus – Single-stranded + RNA virus, enveloped

Symptoms – Typical: Sudden onset of fever with severe joint pain

(often hands/feet), headache, nausea, vomiting, rash, muscle pain

– Joint pain can persist for weeks or months

– Prior to recent outbreaks, no fatal cases

Similar symptoms and range as dengue – misdiagnosed?

Page 28: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

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

Page 29: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

CHIKV Transmission Cycle urban areas Asia, Indian Ocean islands, Europe,

Caribbean

Aedes aegypti & Ae. albopictus

Page 30: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

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

266,000 cases

( IR 34% )

Chikungunya outbreak 2004-2007

Page 31: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Chikungunya Virus Outbreak

878 imported cases to France

Pialoux et. al 2007 Lancet Inf Dis, 7:319-327

Page 32: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Chikungunya outbreak 2004-2007

>1.4 million cases

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

Page 33: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

New emergence in

2007: ~270 cases

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

Chikungunya outbreak 2004-2007

Page 34: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Charrel et al. 2007. N Engl J Med 356;8

Page 35: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

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

– Hot 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/artificial breeding sites

Modified from Chretien JP, Linthicum KJ. Lancet. 2007

Page 36: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

6 December 2013

St. Martin,

French West Indies,

Caribbean

36

Page 37: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Distribution of

CHIKV in the

Americas –

18 months

Page 38: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Asian CHIKV genotype circulating in Caribbean

38

Lanciotti. Emerg Infect Dis.

2014 Aug;20(8):1400-2.

Leparc-Goffart. Lancet. 2014

Feb 8;383(9916):514.

Similar to

strains

circulating in

Asia, Pacific

Islands

Page 39: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

The 2nd perfect microbial storm:

Chikungunya

X A virus from Africa (an alphavirus – Chikungunya)

X A mosquito from Africa (Aedes aegypti)

X (A shipment from the Philippines)

X A completely naïve population

X Outbreak total :

1,722,188, cases

(PAHO 18 Sept 2015)

Page 40: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Outline

Background and concepts

Reasons for epidemic transmission and spread

Emerging mosquito-borne viruses

• West Nile virus

• Dengue virus

• Chikungunya virus

Risk in US

Atlantic Monthly, 1997

Page 41: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Dengue - Risk in U.S.? Imported cases

• 380 laboratory confirmed cases of dengue in 2013

• Became notifiable in 2010

Ae. aegypti & Ae. albopictus occur here (spreading)

Local transmission

– Texas: 1980 (23), 1986 (9), 1995

(7), 1997 (3), 1998 (1),1999 (18),

2005 (25) 2013 (18)

– Hawaii: 2001 (122)

– Florida: 2009-10 (28)

– New York: Suffolk County 2013 (1)

Page 42: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

CHIKV: Future Outlook for the Americas

• Large CHIKV outbreaks in tropical America will continue for several years – Millions of cases likely

– Tens of thousands of travel-associated cases into US

• CHIKV outbreak potential in contiguous US: – Aedes aegypti present:

• Sporadic autochthonous cases continue

• Small focal outbreaks possible

• US-Mexico border could be a problem area

– Only Aedes albopictus present: • Aedes albopictus in Americas are competent vectors

Page 43: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

http://www.cdc.gov/ncidod/dvbid/Arbor/albopic_97_sm.htm

Distribution of Ae. albopictus

in US, year 2000

Page 44: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Ae. albopictus range expansion

Page 45: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue
Page 46: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Exotic Pathogens That Have

Recently Been Introduced to the US

Dengue Fever

West Nile Fever

Yellow Fever

Mayaro Fever

Chikungunya

Ross River

SARS

Influenza

Lassa Fever

Monkeypox

CJD/BSE

HIV/AIDS

Cholera

E. coli O157

Malaria

Leishmaniasis

Chagas Disease

Cyclospora

Page 47: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Exotic Mosquito Species Recently Introduced and

Established in the US

Aedes (Stegomyia) albopictus

Ochlerotatus (Aedes Finlaya) togoi

Ochlerotatus (Aedes Finlaya) japonicus

Aedes bahamensis

Culex biscayensis

Page 48: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Live Animal Importation into the USA

47,000 mammals

28 species of rodents

379,000 birds

2 million reptiles

& poisonous snakes

49 million amphibians

223 million fish

U.S. Fish & Wildlife Service Data (2002)

Page 49: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Factors that Decrease the Risk of Epidemic

Transmission the United States

Living Conditions

• Housing construction

• Window and door screens

• Reliable piped clean water systems

• Air conditioning

Human Behavior

• Social practices

• Television

Human Population Density

Page 50: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Environmental Parameters Limit DENV

(CHIKV) Transmission in the Contiguous States Example: 2005 Outbreak on the US-Mexico Border

50

Am J Trop Med Hyg 2008;78: 364-9

• 8 times more infections in Matamoros

• 4% infected in Brownsville

• 32% in Matamoros

• Substantial Aedes aegypti infestations

in both locations

• Different environmental conditions

• 85% homes air conditioned in

Brownsville; 29% in Matamoros

• Lot size 3 times greater in

Brownsville

• No air conditioning increased dengue

risk 7 fold

• Smaller lot size increased dengue risk

15 fold

Page 51: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

Dengue, West Nile virus, Chikungunya, Zika, Powassan, Heartland, …

WHAT’S NEXT?

Page 52: Global Emergence of Mosquito-borne Viruses · 2015-11-15 · Delayed identification and control of initial outbreaks ... • Large CHIKV outbreaks in tropical America will continue

One World

One Health

Questions?