The Epidemiology and Disease Burden

of Dengue Fever

Duane J Gubler, DirectorSignature Research Program in Emerging Infectious Diseases

Duke-NUS Graduate Medical School, Singapore

and

Asia Pacific Institute of Tropical Medicine and Infectious

Diseases, Honolulu

Flavivirus Vaccination, Annecy, France, 6-8 Dec, 2010

The Epidemiology of Dengue

Global Trends

• Population growth in tropical developing countries

• Economic growth in Tropical developing countries

• Unprecedented urban growth

• Globalization (modern transportation)

Increased movement of people, animals, commodities, vectors and pathogens

• Deterioration of public health infrastructure

Average annual number of DF/DHF

cases reported to WHO, 1955-2007

908 15,497

122,174

295,554

479,848

968,564

0

200000

400000

600000

800000

1000000

1200000

1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2007

Nu

mb

er

of

ca

se

s

0

10

20

30

40

50

60

70

Nu

mb

er

of

co

un

trie

s

Source: DengueNet

2007 data provisional

Expanding geographic

Distribution

Increased epidemic

activity

Hyperendemicity

Emergence of DHF

and increasing

Disease severity

The 20th

Century Re-emergence of Dengue

PNAS, 2004

Global Air Route Network

Commercial Air Traffic Over a 24 Hour Period

DEN-1

DEN-2

Global Distribution of Dengue Virus Serotypes, 1970

Gubler, 1998

Global Distribution of Dengue Virus Serotypes, 2010

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-1

DEN-2

DEN-3

DEN-1

DEN-2

DEN-3

DEN-4 DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

DEN-1

DEN-2

DEN-3

DEN-4

Adapted from Gubler,1998

DEN-4

Re-Emergence of Dengue in the Americas

0 8,822

77,480104,412

266,818

656,240

0

100000

200000

300000

400000

500000

600000

700000

1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2007

Nu

mb

er

of

ca

se

s

0

5

10

15

20

25

30

35

40

45

Nu

mb

er

of

co

un

trie

s

Source: DengueNet

2007 data provisional

DENV-1

DENV-2

DENV-3

DENV-2

DENV-4

DENV-1

DENV-2

DENV-3

DENV-1

DENV-4

DENV-2

DENV-3

DHF DHF DHF

Newly introduced viruses

0

5

10

15

20

25

0

50

100

150

200

250

300

350

1958

1960

1962

1964

1966

1968

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

2002

2004

2006

2008

2010

Morbidity Case fatality

Source: Bureau of EpidemiologyData until 27th March 2010

Year

Morbidity

Morbidity and case fatality rate from DF/DHF/DSS , Thailand, 1958-2010

Case fatality

IR: 67/100.000

pddk

CFR: 0,89%

DHF, Incidence and CFRIndonesia

Dengue Incidence in Sri Lanka, 1989-2009Population Proportion (100,000)

Reported Incidence though passive surveillance :

2000 - 30/100,000 population

2004 - 80/100,000 population

2009 - 170/ 100,000 population

First epidemic of DHF

0

10

20

30

40

50

60

0

50

100

150

200

250

300

350

1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005 2008

Illn

es

s r

ate

s p

er

10

0,0

00

Year

DHF

DF

Premises index

Pre

mis

es

in

de

x

Incidence of DF/DHF in Singapore, 1966-2009

Data from Ministry of Health,

Singapore

0

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Nu

mb

er

of

cases

Year

Number of cases recorded from three WHO regions- SEARO, WPRO and AMRO

AMRO

WPRO

SEARO

0

500

1000

1500

2000

2500

3000

3500

2000 2001 2002 2003 2004 2005 2006 2007 2008AMRO 92 140 255 164 71 159 193 317 585

WPRO 247 510 364 454 572 749 694 1159 674

SEARO 656 1097 1035 1202 1235 1766 1558 1966 1247

Nu

mb

er

of

death

s

Number of deaths reported

16

PDVI Estimates of Expansion Factors

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Total population at risk• 3.6 billion people at risk for symptomatic dengue

• 55% of the world population living in countries at risk

for locally acquired dengue infection

Burden of Dengue

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Total dengue infections

• 270 million dengue infections annually

- 230 million asymptomatic infections

• Social impact of epidemic dengue

Burden of Dengue

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Total symptomatic dengue cases• 34 million cases of dengue fever annually

• 2 million DHF cases annually

Total dengue deaths • 21,000 deaths annually

Burden of Dengue

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

New Dengue Estimates

Deaths

DSS

DHF

Dengue Fever

Asymptomatic Infections

At-Risk Population

21,000

2 million

34 million

230 million?

3.6 billion

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Disease Cases Deaths

Estimated

Countries

Affected

Dengue 36 million 21,000 124

Yellow Fever* 200,000 30,000 >42

Japanese

Encephalitis*

50,000 >10,000>10

Malaria* 500 million >1 million >105

Comparison of dengue burden of disease with other mosquito borne diseases

* Adapted from: E. Callaway. Dengue fever climbs the social ladder. Nature 2007;

448:734-735.

22

Means ( standard deviations) of cost

components per dengue case by study

site*

23

Estimation of average annual national cost of

dengue morbidity and mortality associated with

2001–2005 official reports*

24

Annual costs and DALYs induced by dengue

illness in the Americas in 2010 US$ (2000-

2007)Cost breakdown (%)

Area

Total costs

(millions of

US$)

Ambul.

cases

Hosp.

cases Deaths

Cost per

capita

Cost per

case DALYs

5.4 45.5% 54.5% 0.0% 0.02 $3,154 18 North

America [1.8;10.7] [0;83] [17;100] [0;0] [0.01;0.03] [1684;4138] [7;35]

380.8 75.6% 22.7% 1.6% 2.74 $307 15 424 Central

America &

Mexico [212.1;596.7] [56;86] [12;41] [1;3] [1.53;4.3] [210;398] [11353;20423]

538.6 68.4% 29.2% 2.2% 4.50 $326 20 223 Andean sub-

region [271.3;877.5] [40;84] [14;57] [1;4] [2.27;7.33] [218;414] [13712;28872]

878.2 78.3% 19.5% 2.0% 4.64 $410 26 492 Brazil

[178.8;1996.7] [17;95] [4;76] [1;9] [0.94;10.55] [164;577] [11722;52947]

25.4 74.4% 24.5% 1.1% 0.41 $184 1 658 Southern

cone** [10.1;45.8] [39;90] [9;59] [1;3] [0.16;0.73] [109;227] [856;3009]

321.4 62.2% 31.7% 6.1% 8.29 $713 8 957 Caribbean

[224.5;438] [47;74] [20;46] [4;9] [5.79;11.29] [592;837] [7430;10588]

2,149.8 72.9% 24.4% 2.6% 2.42 $382 72 772 The

Americas [898.4;3965.4] [34;88] [10;61] [1.5;6.8] [1.01;4.47] [236;508] [45080;115874]

Aggregate financing of projected laboratory positive dengue cases by type of

cost and source of financing, average per year (2002-2007)

Source of

financing

Direct medical

costs

Direct non-

medical

costs

Indirect

costs

All types of

costs Row %

Insurance $5,369,180 $0 $0 $5,369,180 25%

Households $1,423,469 $489,180 $6,688,721 $8,601,370 41%

Employers $0 $0 $1,676,545 $1,676,545 8%

Government $4,978,607 $0 $456,641 $5,435,248 26%

Total $11,771,257 $489,180 $8,821,907 $21,082,343 100%

Column % 56% 2% 42% 100%

26

Comprehensive costs of dengue:

Thailand, Panama, and Puerto Rico

Item Thailand Panama

Puerto

Rico

Thailand vs

Panama

Population (million) 62 3.3 3.9

Cost of dengue illness (US $ million) $158 $11.8 $21.1

Per capita cost of illness $2.55 $3.58 $5.41 -29%

Cost of dengue vector control (US $ million) $62 $5.0 $7.7

Per capita cost of vector control $1.00 $1.52 $1.97 -34%

Total cost of dengue (US $ million) $220 $16.9 $28.8

Per capita cost of dengue $3.55 $5.22 $7.38 -32%

Per capita GDP $2,750 $4,630 $17,100 -31%

Dengue / GDP 0.13% 0.11% 0.04% 15%

Vector control share of dengue costs 28% 30% 27% -7%

Thailand based on officially reported cases only, $48 million

Armien B et al.: Am J Trop Med Hyg 2008, 79(3):364–371.

Kongsin S et al.; Dengue Bulletin 2010, in press.

Perez C et al.: Dengue Bulletin 2010, in press.

Halasa Y et al.: Unpublished data

Index mundi, CIA factbook - http://www.indexmundi.com/puerto_rico/gdp_per_capita_(ppp).html

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Non endemic countries:

Risk to Travelers

• 125 million international tourists visited dengue

endemic countries in 2004* (United Nations World

Tourism Organization)

• 7% to 45% of febrile travelers returning from endemic

areas: Serological evidence of recent dengue

infection †

• Prospective study of Dutch travelers: 2.9% developed

symptomatic dengue‡

*http://www.unwto.org/index.php

† Wilder-Smith A, Schwartz E. Dengue in travelers. N Engl J Med. 2005 Sep 1;353(9):924-32.

‡Cobelens FG, Groen J, Osterhaus AD, Leentvaar-Kuipers A, Wertheim-van Dillen PM, Kager PA. Incidence and risk

factors of probable dengue virus infection among Dutch travellers to Asia. Trop Med Int Health. 2002 Apr;7(4):331-8.

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Additional symptomatic dengue

cases from non endemic countries

• 125 million x 0.029

= 3.6 million dengue cases among travelers

Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

What is the Impact of Epidemic Dengue on

Tourism? Commonwealth Games 2010

30

Potential impact of outbreak

on tourist revenuesCountry

or region

Average

expenditure US$

per foreign tourist

(latest period)

Potential impact

on tourism

revenues (US$

million)

Estimated

immediate cost[1]

(US$ million) for

comparison

Gujarat 1725[2] (2007) 7-43 90

Malaysia 857[3] (2007) 57-171 133

Thailand 980[4] (2006) 377-1132 127

[2] Investment Commission of India (2008)

[3] Tourism Malaysia (2008)

[4] Tourism Authority of Thailand (2008)

[1] Immediate cost = cost of illness + cost of intervention programmes as defined

in 1.1

*Tiina Murtola1,2, Tapasvi Puw ar3, Robert Field1, Hong-Fei Gong2, Dileep

Mavalankar3, Donald S. Shepard4, S.S. Vasan1,2. Quantifying the Impact of

Chikungunya and Dengue on Tourism Revenues. 2nd International Conference

on Tourism, Indian Institute of M

Approximate Global Distribution of Dengue and Aedes aegypti, by

State/Province, 2010

Areas with recent dengue transmission

Areas infested with Aedes aegyptiAdapted from Gubler, 1998

Dengue Hemorrhagic Fever

Public Health Impact

Social Impact

Economic Impact

The Epidemiology and Disease Burden of

Dengue Fever

Conclusions

• Dengue has significant public health, economic and social

impact on populations in endemic countries

• Dengue is grossly under reported in most endemic

countries

• Dengue disease burden and cost are likewise grossly

under estimated

• There is a desperate need for good population-based

estimates of the economic cost of dengue

• Surveillance for dengue is very poor in most dengue

endemic countries