The Epidemiology and Disease Burden of Dengue Fever

Duane J Gubler, Director

Signature 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

The 20th Century Re-emergence of Dengue

Average annual number of DF/DHF cases reported to WHO, 1955-2007
1200000 70

Expanding geographic Distribution

Number of cases

1000000

968,564

60

50 800000 40 600000
479,848

Hyperendemicity Emergence of DHF and increasing Disease severity

30

400000
295,554

20

200000
908 15,497

122,174

10

0 1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2007

Source: DengueNet 2007 data provisional

Number of countries

Increased epidemic activity

Global Air Route Network

PNAS, 2004

Commercial Air Traffic Over a 24 Hour Period

Global Distribution of Dengue Virus Serotypes, 1970

DEN-1 DEN-2

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-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

Re-Emergence of Dengue in the Americas

DHF
700000 600000
DENV-2 DENV-1 DENV-3 DENV-2 DENV-3

DHF

DHF
45 40 35 30

656,240
DENV-2 DENV-4 DENV-1
DENV-2 DENV-3 DENV-1 DENV-4

500000 400000 300000 200000 100000

0 8,822 77,480 104,412 266,818

25 20 15 10 5 0 1955-1959 1960-1969 1970-1979 1980-1989 1990-1999 2000-2007

Source: DengueNet 2007 data provisional

Newly introduced viruses

Number of countries

Number of cases

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

3 5 0 3 0 0 2 5 0 2 0 0

M orb id ity
M o rb id ity Ca s efa ta lity

C asefatality

2 5

2 0

1 5

1 5 0
1 0 0 5 0 0

1 0 5 0
6 6 9 1 6 9 9 1
0 6 9 1 2 6 9 1 4 6 9 1 8 6 9 1 0 7 9 1 2 7 9 1 4 7 9 1 6 7 9 1 8 7 9 1 0 8 9 1 2 8 9 1 4 8 9 1 6 8 9 1 8 8 9 1 0 9 9 1 2 9 9 1 4 9 9 1 8 9 9 1 0 0 0 2 2 0 0 2 4 0 0 2 6 0 0 2 8 0 0 2

8 5 9 1

Y ear

Source: Bureau of Epidemiology Data until 27th March 2010

0 1 0 2

Indonesia

DHF, Incidence and CFR

IR: 67/100.000 pddk

CFR: 0,89%

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

First epidemic of DHF

Reported Incidence though passive surveillance : 2000 30/100,000 population 2004 80/100,000 population 2009 170/ 100,000 population

Incidence of DF/DHF in Singapore, 1966-2009

350
DHF

60
DF Premises index

300
Illness rates per 100,000 250 200

50

30 150 20 100 50 0 1966 1969 1972 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005 2008 Year 10

Data from Ministry of Health,

Premises index

40

Number of cases recorded from three WHO regions- SEARO, WPRO and AMRO
1600000
AMRO WPRO

1400000

SEARO

1200000

Number of cases

1000000

800000

600000

400000

200000

0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Number of deaths reported

3500

Number of deaths

3000

2500

2000

1500

1000

500

0
AMRO
WPRO SEARO 2000 92 247 656 2001 140 510 1097 2002 255 364 1035 2003 164 454 1202 2004 71 572 1235 2005 159 749 1766 2006 193 694 1558 2007 317 1159 1966 2008 585 674 1247

PDVI Estimates of Expansion Factors

16

Burden of Dengue
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

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

Burden of Dengue
Total dengue infections
270 million dengue infections annually - 230 million asymptomatic infections Social impact of epidemic dengue

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

Burden of Dengue
Total symptomatic dengue cases
34 million cases of dengue fever annually 2 million DHF cases annually

Total dengue deaths

21,000 deaths annually

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.

Comparison of dengue burden of disease with other mosquito borne diseases

Disease Dengue Cases 36 million Deaths 21,000

Estimated Countries Affected

124

Yellow Fever*
Japanese Encephalitis* Malaria*

200,000
50,000 500 million

30,000
>10,000 >1 million

>42
>10

>105

* Adapted from: E. Callaway. Dengue fever climbs the social ladder. Nature 2007; 448:734-735.
Beatty ME, Letson GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Means ( standard deviations) of cost components per dengue case by study site*

22

Estimation of average annual national cost of dengue morbidity and mortality associated with 20012005 official reports*

23

Annual costs and DALYs induced by dengue illness in the Americas in 2010 US$ (20002007)
Area North America Central America & Mexico Andean subregion Brazil Southern cone** Caribbean Total costs (millions of US$) 5.4 [1.8;10.7] 380.8 [212.1;596.7] 538.6 [271.3;877.5] 878.2 [178.8;1996.7] 25.4 [10.1;45.8] 321.4 [224.5;438] Cost breakdown (%) Ambul. cases 45.5% [0;83] 75.6% [56;86] 68.4% [40;84] 78.3% [17;95] 74.4% [39;90] 62.2% [47;74] Hosp. cases 54.5% [17;100] 22.7% [12;41] 29.2% [14;57] 19.5% [4;76] 24.5% [9;59] 31.7% [20;46] Deaths 0.0% [0;0] 1.6% [1;3] 2.2% [1;4] 2.0% [1;9] 1.1% [1;3] 6.1% [4;9] Cost per capita 0.02 [0.01;0.03] 2.74 [1.53;4.3] 4.50 [2.27;7.33] 4.64 [0.94;10.55] 0.41 [0.16;0.73] 8.29 [5.79;11.29] Cost per case $3,154 [1684;4138] $307 [210;398] $326 [218;414] $410 [164;577] $184 [109;227] $713 [592;837] DALYs 18 [7;35] 15 424 [11353;20423] 20 223 [13712;28872] 26 492 [11722;52947] 1 658 [856;3009] 8 957 [7430;10588]

The Americas

2,149.8 [898.4;3965.4]

72.9% [34;88]

24.4% [10;61]

2.6% [1.5;6.8]

2.42 [1.01;4.47]

$382 [236;508]

72 772 [45080;115874]

24

Aggregate financing of projected laboratory positive dengue cases by type of cost and source of financing, average per year (2002-2007)
Source of financing Insurance Households Employers Government Total Column % Direct medical costs $5,369,180 $1,423,469 $0 $4,978,607 $11,771,257 56% Direct nonmedical costs $0 $489,180 $0 $0 $489,180 2% Indirect costs $0 $6,688,721 $1,676,545 $456,641 $8,821,907 42% All types of costs $5,369,180 $8,601,370 $1,676,545 $5,435,248 $21,082,343 100%

Row % 25% 41% 8% 26% 100%

Comprehensive costs of dengue: Thailand, Panama, and Puerto Rico

Item Population (million) Cost of dengue illness (US $ million) Per capita cost of illness Cost of dengue vector control (US $ million) Per capita cost of vector control Total cost of dengue (US $ million) Per capita cost of dengue Per capita GDP Dengue / GDP Vector control share of dengue costs Thailand Panama 62 3.3 $158 $2.55 $62 $1.00 $220 $3.55 $2,750 0.13% 28% $11.8 $3.58 $5.0 $1.52 $16.9 $5.22 $4,630 0.11% 30% Puerto Thailand vs Rico Panama 3.9 $21.1 $5.41 $7.7 $1.97 $28.8 $7.38 $17,100 0.04% 27% -29%

-34% -32% -31% 15% -7%

Thailand based on officially reported cases only, $48 million Armien B et al.: Am J Trop Med Hyg 2008, 79(3):364371. 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
26

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

on GW, Margolis HS., Phuket, Thailand October 17-19, 2008.

Potential impact of outbreak on tourist revenues

Country Average Potential impact Estimated or region expenditure US$ on tourism immediate cost[1] per foreign tourist revenues (US$ (US$ million) for (latest period) million) comparison Gujarat Malaysia Thailand
1725[2] (2007) 857[3] (2007) 980[4] (2006)

7-43 57-171 377-1132

90 133 127

[1] Immediate cost = cost of illness + cost of intervention programmes as defined in 1.1 [2] Investment Commission of India (2008) [3] Tourism Malaysia (2008) [4] Tourism Authority of Thailand (2008) *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 30

Approximate Global Distribution of Dengue and Aedes aegypti, by State/Province, 2010

Adapted from Gubler, 1998

Areas with recent dengue transmission Areas infested with Aedes aegypti

Public Health Impact Social Impact Economic Impact

Dengue Hemorrhagic Fever

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