Click to edit Master subtitle style 11/03/13 Dengue Update Actualització sobre dengue Ned Hayes, MD Leading research at:
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Dengue Update
Actualització sobre dengueNed Hayes, MD
Leading research at:
11/03/13
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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Estimated Burden of DengueInstitute of Health Metrics
• 11,400 dengue deaths in 1990 (0.215 per 100K)
• 14,700 dengue deaths in 2010 (0.214 per 100K)
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Estimated Burden of DengueInstitute of Health Metrics
• 11,400 dengue deaths in 1990 (0.215 per 100K)
• 14,700 dengue deaths in 2010 (0.214 per 100K)
(Malaria: 1,169,500 deaths in 2010)
(Chagas: 10,300 deaths in 2010)
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Estimated Burden of DengueInstitute of Health Metrics
• 11,400 dengue deaths in 1990 (0.215 per 100K)
• 14,700 dengue deaths in 2010 (0.214 per 100K)
(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
Gubler DJ. Trop Med and Health, 2011
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Reported Cases of Dengue:
Thailand
Indonesia
Vietnam
Gubler DJ. Trop Med and Health, 2011
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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
Gubler DJ. Trop Med and Health, 2011
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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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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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