DENGUE: EPIDEMIOLOGY PART II. SCOTT B HALSTEAD, MD. Director, Research PEDIATRIC DENGUE VACCINE INITIATIVE. EPIDEMIOLOGY. Risk factors for severe disease. Sequential dengue infection (includes antigenic structure of virus) Race Age Host genetic factors Nutritional status Sex. Race.
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SCOTT B HALSTEAD, MD
PEDIATRIC DENGUE VACCINE INITIATIVE
At least 5:11,2
DENGUE NEUTRALIZING ANTIBODIES BY AGE IN 210 CHILDREN RESIDENT
IN PORT AU PRINCE, HAITI, 1996.
N =(46) (40) (36) (41) (27) (13) (10) (4)
DHF - EFFECT OF AGE, 1981 Cuba Outbreak
GUZMAN MG et al. Int J Infect Dis 6:18, 2002
Gamble J et al. Biochem Soc Med Res Soc 98:211-6, 2000.
HLA1: HLA-A*0207 HLA-A*0203
HLA A24 HLA A33
Vit D2: t allele/352
DCSIGN4: CD 209 promoter
TNFα5: TNF 308
1. Loke H et al. JID 184:1369-73, 2001
2. Stephens HA et al. Tissue Antigens 60:309-318, 2002.
3. Loke H et al. AJTMH 67:102-6, 2001
4. Sakuntabthai A et al. Nat Genetics 37:507-13, 2005
5. Fernandez-Mestre MT et al. Tissue Ag 64:468-72, 2004
Effect of nutritional status on dengue disease severity1
Well nourished children:
highly susceptible to severe disease
Malnourished: protected against severe disease (protein-calorie malnutrition grade 2 and 3)
1. Thisyakorn U et al. CID 16:295-297, 1993
DSS in a 6 month-old infants with hepatomegaly. Vietnam
WHY DO MATERNAL ANTIBODIES ENHANCE DENGUE DISEASE?
CENTRAL ROLE OF MACROPHAGES IN SUPPORTING DENGUE INFECTIONS IN HUMANS
Dengue viruses are adapted to grow in dendritic cells,
monocytes and macrophages.
Complexed with antibodies dengue viruses enter FcR-bearing cells with great efficiency.
IMMUNE ENHANCEMENT OF DENGUE INFECTION(Antibody-Dependent Enhancement)
LIBRATY DH et al JID 185:1213, 2002
Schematic distribution of dengue 2 viruses
in blood and tissues of 31 rhesus monkeys.
DENGUE VIRUSES, BANGKOK 1973 - 2001