Dengue epidemiology part ii l.jpg
This presentation is the property of its rightful owner.
Sponsored Links
1 / 37

DENGUE: EPIDEMIOLOGY PART II PowerPoint PPT Presentation


  • 467 Views
  • Uploaded on
  • Presentation posted in: General

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.

Download Presentation

DENGUE: EPIDEMIOLOGY PART II

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Dengue epidemiology part ii l.jpg

DENGUE:EPIDEMIOLOGYPART II

SCOTT B HALSTEAD, MD

Director, Research

PEDIATRIC DENGUE VACCINE INITIATIVE


Epidemiology l.jpg

EPIDEMIOLOGY

  • Risk factors for severe disease.

    • Sequential dengue infection (includes antigenic structure of virus)

    • Race

    • Age

    • Host genetic factors

    • Nutritional status

    • Sex


Slide3 l.jpg

Race

  • Caucasian & Asian vs African.

    At least 5:11,2

  • Guzman MG et al. AJTMH 42:179-184, 1990.

  • Halstead SB et al AJTMH 65:180, 2001


Blacks are relatively resistant to severe dengue illness l.jpg

BLACKS ARE RELATIVELY RESISTANT TO SEVERE DENGUE ILLNESS

  • A human resistance gene seems to explain the observation that while all dengue virus types circulate in Africa no DHF/DSS cases or outbreaks of DF have been reported.


Race santiago de cuba outbreak 1997 l.jpg

RACE - SANTIAGO DE CUBA OUTBREAK, 1997


Slide7 l.jpg

DENGUE NEUTRALIZING ANTIBODIES BY AGE IN 210 CHILDREN RESIDENT

IN PORT AU PRINCE, HAITI, 1996.

N =(46) (40) (36) (41) (27) (13) (10) (4)


Slide8 l.jpg

AGE


Slide9 l.jpg

DHF - EFFECT OF AGE, 1981 Cuba Outbreak

GUZMAN MG et al. Int J Infect Dis 6:18, 2002


Slide10 l.jpg

CAPILLARY FRAGILITY

Gamble J et al. Biochem Soc Med Res Soc 98:211-6, 2000.


Genetic associations susceptibility resistance l.jpg

GENETIC ASSOCIATIONSSusceptibility Resistance

HLA1: HLA-A*0207 HLA-A*0203

HLA-B*51 HLA-B*52

HLA A24 HLA A33

Vit D2: t allele/352

FcRγII3:

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


Nutritional status l.jpg

NUTRITIONAL STATUS


Nutritional status of dhf cases vs controls l.jpg

NUTRITIONAL STATUS OF DHF CASES vs. CONTROLS


Slide14 l.jpg

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


Slide15 l.jpg

SEX


Sex ratios by dengue syndrome bangkok children s hospital 1962 64 l.jpg

SEX RATIOS BY DENGUE SYNDROMEBangkok Children’s Hospital, 1962-64


Dhf dss during primary dengue infections l.jpg

DHF/DSS during primary dengue infections.


Dhf dss in infants identical to but more severe than dhf dss in children l.jpg

DHF/DSS in infants, identical to but more severe than DHF/DSS in children

  • Higher case fatality rates, resuscitation requires more fluid per Kg body weight than in older children with 2o infection.

    • Hung NT et al AJTMH 72:370, 2005

  • Circulating cytokines and cytokine levels during acute phase similar to those in older children during 2o infection.

    • Hung NT et al JID 189:221, 2004


Slide19 l.jpg

DSS in a 6 month-old infants with hepatomegaly. Vietnam


Infant dhf dss l.jpg

INFANT DHF/DSS


Why do maternal antibodies enhance dengue disease l.jpg

WHY DO MATERNAL ANTIBODIES ENHANCE DENGUE DISEASE?

CENTRAL ROLE OF MACROPHAGES IN SUPPORTING DENGUE INFECTIONS IN HUMANS


Slide23 l.jpg

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 a ntibody d ependent e nhancement l.jpg

IMMUNE ENHANCEMENT OF DENGUE INFECTION(Antibody-Dependent Enhancement)

  • In the presence of dengue ADE antibody:

  • increased rate of infection

  • increase in the number of infected cells.

  • increased production of viruses per cell.


Ade in human dengue den virus load and disease severity l.jpg

ADE IN HUMAN DENGUE: DEN virus load and disease severity


Slide26 l.jpg

DEN 3

VIREMIA

●--● DSS

▲- ▲DHF

□--□ DF

LIBRATY DH et al JID 185:1213, 2002


Disease severity correlates with cellular infection l.jpg

DISEASE SEVERITY CORRELATES WITH CELLULAR INFECTION


Slide28 l.jpg

Schematic distribution of dengue 2 viruses

in blood and tissues of 31 rhesus monkeys.


In endemic areas dhf dss annual outbreaks differ in severity and size l.jpg

In endemic areas, DHF/DSS annual outbreaks differ in severity and size.


Myanmar varying cfr l.jpg

MYANMAR: VARYING CFR


Slide32 l.jpg

DENGUE VIRUSES, BANGKOK 1973 - 2001


Slide33 l.jpg

WHY?

  • Possible effect of

    • ADE

    • Heterotypic immunity

    • Replacement of serotypes

    • Clade extinctions

  • These possibilities have been explored in mathematical models, most are based upon the hospital epidemiological data from Bangkok or all of Thailand.


Effect of ade on epidemic cycles l.jpg

EFFECT OF ADE ON EPIDEMIC CYCLES

  • “Enhancement of infection may generate a complex and persistent cyclical or chaotic epidemic behavior ….and coexistence of mutiple strains”

    • Ferguson N et al. The effect of antibody-dependent enhancement on the transmission dynamics and persistence of mutiple-strain pathogens.Proc Natl Acad Sci USA 96:790-4, 1999


Effect of heterotypic immunity on epidemic cycles l.jpg

EFFECT OF HETEROTYPIC IMMUNITY ON EPIDEMIC CYCLES

  • 8-10 year epidemic cycles are accompanied by clade extinctions.

  • Mathematical model suggests that heterotypic immunity is responsible.

    • Adams B et al PNAS 103: 14234-9, 2006


Serotype replacement l.jpg

SEROTYPE REPLACEMENT

  • DENV -1 replaced DENV 2, 3, 4. Related to stochastic event due to low transmission in 1999-2000?

    • Thu HM et al. Myanmar denge outbreak associated with displacement of serotypes 2, 3 and 4 by dengue 1. Emerg Infect Dis 10:693-7, 2004.


Clade extinctions due to stochastic events l.jpg

CLADE EXTINCTIONS DUE TO STOCHASTIC EVENTS

  • In Myanmar, clades B and C of genotype I DENV -1 circulated with clade A genotype III during the 1990s. After 1998, clade A disappeared leaving only clades B and C.

    • Thu HM et al Lineage extinction and replacement in dengue type 1 virus populations are due to stochastic events rather than to natural selection. Virol 336:163-72, 2005.

  • In Thailand, clades of DENV -3 circulating prior to 1992 disappeared and were replaced by two lineages with common ancestor.Earlier extinctions, 1963, 1973?

    • Wittke V et al. Extinction and rapid replacement of strains of dengue 3 virus during an interepidemic period. Virol 301:148-156, 2002.


  • Login