dengue update actualització sobre dengue€¦ · 11/03/13 refining the global spatial limits of...

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11/03/13

Dengue Update

Actualització sobre dengueNed Hayes, MD

Leading research at:

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Dengue

• Caused by infection with one of 4 viruses

� DEN-1, DEN-2, DEN-3, DEN-4

• Characterized by fever, headache, myalgia, thrombocytopenia, sometimes bleeding

� Severe forms can have severe bleeding and/or shock

• Transmitted primarily through bite of Aedes

aegypti, Aedes albopictus, other Aedes species

• Prevention is through vector control, personal protection against mosquito bites



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How much dengue is there ?

Quant dengue hi és?


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Estimated Burden of Dengue

� 3,970,000,000 people living in areas of risk

� 36,000,000 dengue cases each year

� 21,000 dengue deaths each year


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Lancet: December, 2012Institute of Health Metrics

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Estimated Burden of DengueInstitute of Health Metrics

• 11,400 dengue deaths in 1990

• 14,700 dengue deaths in 2010

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• 11,400 dengue deaths in 1990 (0.215 per 100K)


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(Malaria: 1,169,500 deaths in 2010)

(Chagas: 10,300 deaths in 2010)

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(Malaria: 1,169,500 deaths in 2010)

(Chagas: 10,300 deaths in 2010)

• 712,000 DALYS in 1990

• 825,000 DALYS in 2010

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Where is there dengue ?

On hi ha dengue?


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Global Distribution of Dengue and Risk of Dengue, 2011

Gubler DJ. Trop Med and Health, 2011

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Refining the Global Spatial Limits of Dengue VirusTransmission by Evidence-Based Consensus

Oliver J. Brady1,2*, Peter W. Gething1, Samir Bhat t1, Jane P. Messina1, John S. Brownstein3,

Anne G. Hoen4, Catherine L. Moyes1, Andrew W. Farlow1, Thomas W. Scot t5,6, Simon I. Hay1,6*

1 Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom, 2 Oxitec Ltd., Abingdon, United Kingdom,

3 Department of Pediatrics, Harvard Medical School and Children’s Hospital Informatics Program, Boston Children’s Hospital, Boston, Massachusetts, United States of

America, 4 Department of Community and Family Medicine, Dartmouth College, Hanover, New Hampshire, United States of America, 5 Department of Entomology,

University of California Davis, Davis, California, United States of America, 6 Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of

America

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How is dengue changing ?

Com es canvia el dengue?


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Distribution of Aedes aegypti in the Americas


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Reported Cases of Dengue:

Thailand

Indonesia

Vietnam


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Distribution of Dengue Serotypes in 1970 Guzman et al. Nature Reviews 2010, after Gubler

DEN-1

DEN-2

DEN-1

DEN-2

DEN-1

DEN-2

DEN-3

DEN-4

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Distribution of Dengue Serotypes in 2004 Guzman et al. Nature Reviews 2010, after Gubler

DEN-1

DEN-2DEN-1

DEN-2

DEN-3

DEN-4DEN-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-4

b


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Why is dengue occurrence changing ?

Per què està canviant l'aparició del dengue?



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Mean Annual Number of Global Airline Passengers



11/03/13 United Nations, Dept of Economic and Social Affairs. http://esa.un.org/unpd/wup/index.htm

Porcentaje de la población mundial residente en zonas urbanas, 1950 y

2010


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Can we control dengue?

Podem controlar el dengue?


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The Lancet, Sept 2012

Primary objective: To assess efficacy of the vaccine against

virologically confirmed, symptomatic dengue occurring one month or more after complete vaccination.

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Methods

• 2452 vaccinated children aged 4 to 11 years, compared (ATP) to 1221 controls who received rabies vaccine or placebo

• Active surveillance for febrile illness

• PCR and NS1 antigen testing on acute serum

• Case of dengue defined as febrile illness with positive dengue PCR or positive NS1 antigen

• Second serum to assess immune response

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Results

• Vaccine efficacy against virologically confirmed dengue was 30% (-13%-57%)

� DEN-1 efficacy: 56% (-22%-84%)

� DEN-2 efficacy: 9% (-75%-51%)

� DEN-3 efficacy: 75% (-375%-100%)

� DEN-4 efficacy: 100% (25%-100%)

• DEN-2 accounted for 59% of all 134 cases

• Immunogenic against all serotypes, including DEN-2

• Good safety profile

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Possible Reasons for Limited Vaccine Efficacy

• Neutralizing antibody as assayed not sufficient to provide good protection ?

• Antigenic mismatch between vaccine epitopes and the pathogenic DEN-2 virus strain ?

• Need for nonstructural genes in vaccine?


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Is dengue a threat to Europe ?

És el dengue una amenaça per a Europa?


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Recent Outbreaks of Particular Interest to Europe

• 2009: Cape Verde Islands: 17,000 cases

• 2010: France: 2 cases

� Hundreds of imported cases each year

• 2010: Croatia: 2 cases (15 infections?)

� <10 ? imported cases each year

• 2012-2013: Madeira Island, Portugal

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Dengue on Madeira

• 3 October: Dengue confirmed in two cases with no relevant travel history

� Virus identified as DEN-1

• 25 November: cumulative total 1891 cases

� 111 patients hospitalized, no fatalities

� Majority had fever, headache, myalgia, arthralgia

• 77 cases of dengue in travelers to mainland Europe/UK from Madeira

• Apparent vector: Aedes aegypti (2005)

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Reported Dengue by Age Group, Madeira Oct 3- Nov 25, 2012

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Nº de casos de novos casos de dengue notificados por semana na Ilha da Madeira, 2012-2013

Fonte: IASaúde, IP-RAM

9

145173

219

395

164

252

315

219

10257

53 24 9 8 10 5 2 30

50

100

150

200

250

300

350

400

450

39 40 41 42 43 44 45 46 47 48 49 50 51 52 1 2 3 4 5

Semanas de 2012 e 2013

Nº de casos


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Gracies !


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