Dengue and Yellow Fever: the Anatomy of Decline and ... · • Typhoid fever • Leptospirosis •...
Transcript of Dengue and Yellow Fever: the Anatomy of Decline and ... · • Typhoid fever • Leptospirosis •...
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
1The screen versions of these slides have full details of copyright and acknowledgements
Dengue and Yellow Fever: The Anatomy of Decline and Emergence
1
Duane J. Gubler, Professor and DirectorSignature Research Program in Emerging Infectious Diseases
Duke-NUS Graduate Medical School, Singapore and
Asia-Pacific Institute of Tropical Medicine and Infectious Diseases, John A Burns School of Medicine,
University of Hawaii, Honolulu
Dengue and yellow fever: decline and emergence
Background on epidemiology and clinical
Yellow fever decline
Re-emergence of dengue
2
Re emergence of dengue
Reasons for re-emergence of dengue
Re-emergence of yellow fever?
Possible explanations for the lack of yellow fever re-emergence
Yellow fever and dengue viruses
Family: Flaviviridae
Genus: Flavivirus
Yellow fever virus; Prototype flavivirus
Dengue viruses
3
Dengue viruses
Serotypes: Denv-1Denv-2Denv-3Denv-4
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
2The screen versions of these slides have full details of copyright and acknowledgements
Nonstructural geneFlavivirus phylogeny
Mosquito-borne
JEMVE
WNSLE
ROCILH
BAGBSQIGUKOK
KEDZIKA
DEN1
4
Tick-borne
No vector
Insect0.1
DEN3DEN2
DEN4YF
SEPENT
LITBE
LGTALK
DTPOW
RBMML
MODAPOI
KRVCFA
TB
Yellow fever and dengue virus genome
5Kuhn, et al., 2006
AfricaTransmission cycles of yellow fever
Monkey
Ae. africanus
Enzootic zone
HumanHuman
Ae. furcifer
Zone of emergence
Ae. aegypti
Epidemic zone
etc.
?Trans-ovarial
Trans-ovarialMonkey
6
Monkey
Ae. africanus
Monkey Human
Ae. furcifertayloriluteocephalusopokafricanussimps. nietc.
Other vertebrate?monkey
Tick(Amblyomma)
TickAe. aegypti
Known part of cycleSpeculative part of cycle
trans-mission
trans-mission
Monkey
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
3The screen versions of these slides have full details of copyright and acknowledgements
Yellow fever transmission cycle in the Americas
Monkey
Haemagogus
T i l Monkey TransovarialHuman Human
Ae. aegypti
7
Monkey Marmoset
Haemagogus
Transovarial yMarmosetTransovarialHuman Human
Ae. aegypti
Urban cycleJungle cycle
Transmission and maintenance cycles of dengue viruses
Aedes Mosquitos
Aedes Mosquitos
Primates Primates Humans Humans HumansHumansVertical
transmissionVertical
transmissionVertical
transmission
Aedes Mosquitos
8
Aedes aegyptiAedes MosquitosAedes
Mosquitos
Aedes aegypti
9
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
4The screen versions of these slides have full details of copyright and acknowledgements
Principal urban vector of DEN and YF
Vector: Aedes aegypti
Biology:
Urban
10
Day biting
Breeds in domestic water
Preferentially bites man
Highly efficient epidemic vector
Aedes aegypti
11
12
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
5The screen versions of these slides have full details of copyright and acknowledgements
Disease: the original viral hemorrhagic fever, a systemic illness with
High viremia
Yellow fever
13
Hepatic, renal, myocardial injury
Hemorrhage
Shock syndrome
Case fatality, 20%
Dengue hemorrhagic fever
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm3 or less)
14
p ( )
Objective evidence of vascular leakage
Case fatality rate: average 5%
Pan American Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Preventionand Control; PAHO: Washington, DC, 1994: 13
Differential diagnosis of dengue and yellow fever
Influenza
Measles
Rubella
M l i
15
Malaria
Typhoid fever
Leptospirosis
Rickettsial infections
Bacterial sepsis
Other viral hemorrhagic fevers
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
6The screen versions of these slides have full details of copyright and acknowledgements
16
Yellow fever history 1600s - Virus, vector introduced from Africa
1648 - Yucatan epidemic, Mayan records
1750 - Term yellow fever first used in Barbados
18th-19th Centuries - major epidemics, Americas, Europe, West Africa
1900 - Reed demonstrates filterable virus transmitted by Ae. aegypti; vector control begins
17
ecto co t o beg s
1904-1912 - Yellow fever controlled in Cuba and Panama
1905 - Last outbreak in U.S. (New Orleans)
1927 - Virus isolated in Africa
1932 - YF jungle transmission cycle (Brazil, then Africa) sylvatic mosquitoes and non-human primates
1936 - Yellow fever vaccine developed
1946 - Aedes aegypti eradication program in Americas
Importance of the 1890s
Filterable agent (=virus) as cause of animal disease
Malaria transmission by mosquito
Discovery of extrinsic incubation period
18
y p
Yellow fever transmission by Ae. aegypti
Spanish-American War
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
7The screen versions of these slides have full details of copyright and acknowledgements
19
Urban yellow fever epidemics in the United States 1793-1905
1. Philadelphia, 1793; 5,000 dead
2. New York City, 1795; 730 dead
3. Boston, New York City and Philadelphia; 1798; more than 5,000 dead
4. Baltimore, 1800; 1,200 dead
5. New Orleans, 1853; 8000 or more dead
20
6. Norfolk, 1855; 2,000 dead
7. Mississippi Valley, 1878; 20,000 dead
8. Cuba, 1898; hundreds dead
9. New Orleans, 1905; more than 900 dead
Currently:
Rare imported cases with travel history
No local transmission
21
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
8The screen versions of these slides have full details of copyright and acknowledgements
Reported cases of yellow fever 1948-98
22WHO Report, 2000
19701930's 2010
Aedes aegypti distribution in the Americas
23Adapted from Gubler, 1998
Dengue: a historical perspectiveMore important epidemics of dengue-like illness
China - 992
Caribbean - 1635
Panama - 1699
Spain/Africa - 1700s
Batavia, Indonesia - 1779
24
Cairo, Egypt - 1779
Philadelphia, PA, USA - 1780
Spain - 1801
Cuba - 1828
Americas and Asia-Pacific - 1800s & early 1900s
World War II - 1941-45
Aedes aegypti eradication program in Americas, 1946
Post war era - 20th Century re-emergence
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
9The screen versions of these slides have full details of copyright and acknowledgements
Epidemic dengue hemorrhagic fever / dengue shock syndrome emerged as newly recognized
disease in Southeast Asia in the 1950s
At the end of WWII all four serotypes of dengue were widespread in Asia
25
1950-1969 1970-1979
Expanding geographic distribution of epidemic dengue/dengue hemorrhagic
fever in Asia
26
1980-2010
Adapted from Gubler, 1998
19701930's 2010
Aedes aegypti distribution in the Americas
27Adapted from Gubler, 1998
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
10The screen versions of these slides have full details of copyright and acknowledgements
The emergence of dengue hemorrhagicfever in the Americas
Prior to 1981 1981-2010
28Adapted from Gubler, 1998
Re emergence of dengue in the US 1980
29
Re-emergence of dengue in the US 1980
Year
1980
1986
1995
1997
1998
Location
Texas
Texas
Texas
Texas
Texas
No. Cases
27
9
7
3
1
Autochthonous dengue in the United States
30
1998
1999
2001
2005
2007
2009
2010
Texas
Texas
Hawaii
Texas
Texas
Florida
Florida
1
17
122
25
?
27
16
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
11The screen versions of these slides have full details of copyright and acknowledgements
Dengue fever in AfricaPrior to 1980 1981-2010
31Areas at riskAdapted from Gubler, 1998Epidemic transmission
Expanding geographic distribution
Increased epidemic activity
Hyperendemicity
The 20th century re-emergence of epidemic dengue
1,151,300
50
60
70
1000000
1200000
1400000
Average annual number of DF/DHF cases reported to WHO, 1955 - 2008
ries
ses
32Source: DengueNet2008 data provisional
Emergence of DHF
908 15,497
122,174
295,554
479,848
0
10
20
30
40
0
200000
400000
600000
800000
1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2008
Number of cases
Num
ber o
f cou
ntr
Num
ber o
f cas
Approximate global distribution of dengue and Aedes aegypti, by state/province, 2010
33Areas with recent dengue transmissionAreas infested with Aedes aegyptiAdapted from Gubler, 1998
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
12The screen versions of these slides have full details of copyright and acknowledgements
Public health impact of dengue
2.5-3 billion people live in areas of risk
50-100 million cases/infections/year
Millions hospitalized
500,000 cases of dengue hemorrhagic fever
34
20,000 plus deaths
Incidence and geographic range are increasing
Economic impact
No vaccine or antiviral drugs
Mosquito control has been largely ineffective
Why have we seen such a dramatic increase in epidemic dengue/dengue
hemorrhagic fever?
Complacency, Lack of political will
Policy changes
35
Changes in public health
Changing life styles/behavior
Microbial adaptation
Technology
Climate change?
Why have we seen such a dramatic increase in epidemic dengue/dengue
hemorrhagic fever?
Demographic changes (Pop. growth and distribution)
Environmental change
Major drivers
36
Environmental change
Uncontrolled urbanization
Modern transportation (Globalization)
Increased movement of people, animals, commodities
Lack of effective mosquito control
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
13The screen versions of these slides have full details of copyright and acknowledgements
33.5
44.5
5
of p
eopl
e
Estimated number of people living in urban areas
37
00.5
11.5
22.5
3
1950 1985 2000 2030
Bill
ions
o
Source: UN
The urban and rural population of the world 1950-2030
38
UrbanizationThe case of Dhaka, Bangladesh
e (M
illio
ns) 14,000,000
10 000 00012,000,00014,000,00016,000,000
39
Num
ber o
f peo
ple
Source: UN
1,500,000
02,000,0004,000,0006,000,0008,000,000
10,000,000
1970 2008
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
14The screen versions of these slides have full details of copyright and acknowledgements
Emergence of dengue/dengue hemorrhagic fever
Uncontrolled urbanization
Crowding
Living conditions
Lack of basic services:
40
Lack of basic services: inadequate housing, piped water, sewage and waste management
From: PAHO, 1997; Gubler, 1998
Urban agglomerations, 1950, 2000, 2015
41Source: UN, World Urbanization Prospects, The 1999 Revision
5 million & over since 1950
5 million & over since 2000
5 million & over in 2015 (projected)
0
204060
80100120
1950 2000 2015
Asia
S. America
Sub-Sahara Africa
ulat
ion
(Milli
ons)
Urban population growth and reported dengue cases
Dengue C1500
2000
2500
3000
600000
800000
1000000
1200000
42Population data, UN; Dengue data, WHO, to April, 2008Estimated Number of People Living in Urban Areas - World
Urb
an P
opu ases
Dengue/DHF - Average Annual Number of Cases Reported to WHO - World
0
500
1000
1950s 1960s 1970s 1980s 1990s 2000s0
200000
400000
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
15The screen versions of these slides have full details of copyright and acknowledgements
Dengue viruses & mosquitoes:
43
hitching a ride on modern transportation
The global airline network
44PNAS, 2004
500
600
700
seng
ers
Mean annual number of airline passengers by decade, United States, 1954-2007
45
0
100
200
300
400
1950s 1960s 1970s 1980s 1990s 2000s
Mill
ions
of p
as
Source: RITA, DOT
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
16The screen versions of these slides have full details of copyright and acknowledgements
46
Global movement of dengue (1971-1980)
47DENV 1; DENV 2; DENV 3; DENV 4
1980
1979
Global movement of dengue (1981-1990)
48DENV 1; DENV 2; DENV 3; DENV 4
1985
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
17The screen versions of these slides have full details of copyright and acknowledgements
Global movement of dengue (1991-2000)
1994
49DENV 1; DENV 2; DENV 3; DENV 4
1994
Global distribution of dengue virus serotypes, 1970
50Gubler, 1998
DEN-2DEN-1
DEN-1DEN-2
DEN-1DEN-2DEN-3DEN-4
Global distributionof dengue virus serotypes, 2010
DEN-1
51Adapted from Gubler,1998
DEN-1DEN-2DEN-3DEN-4
DEN-1DEN-2DEN-3DEN-4
DEN-1DEN-2DEN-3DEN-4
DEN-2DEN-3DEN-4
DEN-1DEN-2DEN-3
DEN-1DEN-2DEN-3DEN-4DEN-1
DEN-2DEN-3DEN-4
DEN-1DEN-2DEN-3DEN-4
DEN-1DEN-2DEN-3DEN-4
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
18The screen versions of these slides have full details of copyright and acknowledgements
Yellow fever: re-emergence?
Low YF vaccine coverage rates
Increased global travel
52
Reinfestation by Aedes aegyptiof urban areas threatens major population centers
Encroachment of humans into sylvatic cycleHuman migration and urbanization
Number of yellow fever cases and deaths reported to WHO, by decade, 1950-1999
12000140001600018000
53
02000400060008000
10000
1950-59 1960-69 1970-79 1980-89 1990-99
Cases Deaths
19701930's 2010
Aedes aegypti distribution in the Americas
54Adapted from Gubler, 1998
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
19The screen versions of these slides have full details of copyright and acknowledgements
Potential for urban yellow fever epidemics
55
in the Americas
Imported yellow fever
Texas 2002
Belgium 2000
California 1999
G 1999
56
Germany 1999
Switzerland 1996
Tennessee 1996
Urban yellow fever, Santa Cruz, BoliviaDec 1997 - June 1998
Six acute cases confirmed
Two clusters of transmission
57
Five died
(Three cases likely contracted infection in the city)
Serosurvey - 281
16 (6%) had YF antibody
5 - no previous immunization
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
20The screen versions of these slides have full details of copyright and acknowledgements
Dados Gerais:
Endemic areas:States: 12
Epidemiologic distribution of yellow fever, Brazil
AM
AC RO TOAL
PE
MA
PI
CERN
PB
RR
PA
AP
58
Population: 27,014,229
Epizootic area :States parts of 3Population 10,443,215
YF free area :States: 15
Fonte: SUCAM/MS Vasconcelos, P.F. (1997)
Enzootic Area
Epizootic Area
YF Free Area
RO
MT
MS
TOBA SE
MG
RS
SP
PR
SC
ES
RJ
GODF
Feb 1
Feb 6
Feb 15
Distribution of confirmed cases of yellow fever by date of onset of symptoms, Laurelty, Paraguay, 2008
59
Jan 11
Feb 2
Feb 4
Feb 8
Feb 1Feb 17
Feb 28
Hypothesis to explain the absence of urbanyellow fever epidemics in the Americas
Cross-protective flavivirus immunity Evidence through monkey experiments
Vi Ad t ti
60
Virus Adaptation Humans
Aedes aegypti
Evolutionary exclusion
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
21The screen versions of these slides have full details of copyright and acknowledgements
Hypothesis to explain the absence of yellow fever in Asia
A matter of logistics
Cross-protective flavivirus immunity
Low vector competence of Asian Aedes aegypti
61
Low vector competence of Asian Aedes aegypti
Geographic and demographic obstacles to spread yellow fever virus
Evolutionary exclusion
Potential global spread of urban yellow fever
62
Dengue and yellow fever viruses
Summary
Both old diseases
Both effectively controlled
63
Dengue re-emerged; yellow fever did not
Dengue viruses evolved with urbanization
Yellow fever remained in the jungle
Current global threat
-
Dengue and Yellow Fever: the Anatomy of Decline and Emergence
Duane J Gubler
22The screen versions of these slides have full details of copyright and acknowledgements
64