DENGUE: EPIDEMIOLOGY PART 1 - PowerPoint PPT Presentation

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DENGUE: EPIDEMIOLOGY PART 1

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Title: DENGUE: EPIDEMIOLOGY PART 1


1
DENGUEEPIDEMIOLOGYPART 1
SCOTT B HALSTEAD, MD
Director, Research PEDIATRIC DENGUE VACCINE
INITIATIVE
2
TRANSMISSION
  • Aedes aegypti breeds in clean water in and around
    houses.
  • Daytime biting.
  • Transmission from human to human requires the
    same female mosquito to bite a viremic human and
    then bite a susceptible human at an interval of
    around 10-12 days.

3
FOUR VIRUSES
  • Life time immunity follows infection to one type.
  • Second, third and possibly four infections are
    possible.
  • CHILDREN first infections are mild, largely
    inapparent.
  • ADULTS - first infections may produce DF, some
    viruses more overt than others.

4
PRIMARY INFECTIONSClinical Features
  • In children
  • DEN 1 3 mild illness
  • DEN 2 4 no illness
  • In adults
  • DEN 1 3 Disease/Infection 1 g.i.
    hemorrhages may accompany peptic ulcer disease.
  • DEN 2 4 - mild - moderate

5
DENGUE FEVER
  • Incubation period 5 days
  • Fever 5 days
  • Leukopenia
  • Moderate thrombocytopenia

Simmons et al Phil J Sci 441-252, 1931
6
DENGUE 1 MACULO- PAPULAR RASH. Day 5 after onset
of fever.
7
DISEASE SPECTRUMMILD SEVEREDF
DHF Thrombocytopenia
ThrombocytopeniaHidden Vasc. Perm1?
Overt Vasc. Perm.1. Wills BA et al J Infect
Dis 190810-818, 2004
8
DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROME
(DHF/DSS)Dengue vasculopathy
9
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10
DSS GRADE IV
11
DSS GRADE III
12
WHY IS DENGUE SUCH A BIG PROBLEM TODAY?
  • Global population growth
  • Rural to urban migration
  • Growth of cities
  • Deterioration of cities
  • Jet travel
  • Health services poorly organized/ underfunded
  • Lack of vector control professionals

13
Global Spread of Dengue
50-100 million infections/year
Aedes aegypti
Countries with active dengue
14
WHY TWO SYNDROMES, BENIGN and SEVERE?
  • Observed in two immunological settings.
  • Primary infections in infants.
  • 2. Secondary infections in children
  • and adults.

15
Two-infections The epidemiological data
  • DHF documented in children (gt 1 yr) who circulate
    infection-acquired dengue antibody. Four
    prospective cohort and 6 prospective
    population-based studies.
  • In most studies, DHF comprises 2-5 of secondary
    infections

16
DHF IN CHILDREN PROSPECTIVE COHORT STUDIES
17
DHF IN CHILDREN PROSPECTIVE POPULATION-BASED
STUDIES
18
DHF IN CHILDREN PROSPECTIVE POPULATION- BASED
STUDIES
19
SEQUENTIAL DENGUE INFECTIONS
Two infections can occur in twelve possible
combinations.
20
Established second infection sequences leading to
DHF
  • 2 1 Thailand Indonesia
  • 3 1 Thailand
  • 1 2 Cuba, 1981 Cuba 1997 Thailand
  • 3 2 Thailand
  • 4 2 Thailand
  • 1 3 Cuba, 2001 Thailand Indonesia
  • 2 3 Thailand, DF in Cuba
  • 1 4 Thailand
  • 2 4 Indonesia
  • 3 4 Thailand

21
No data
  • 4 1
  • 4 3

KALAYANROOJ S et al AJTMH 2008 in press.
22
Third infections resulting in DHF
  • 1 3 2 Thailand

MAMMAN MP personal communication
No DHF
  • 1 2 3 Cuba, 2001.

GUZMAN MG personal communication
23
DENGUE VIRUSES, BANGKOK 1973 - 2001
24
Lags at Which Correlation Between Bangkok and
other Provinces Is Maximized
plt1e-8 148 km/month
(months)
25
DHF AT BANGKOK CHILDRENS HOSPITAL
1O INFECT.
2O INFECTIONS
26
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27
Fischer and Halstead Yale J Biol Med
42329-349,1970
28
Fischer and Halstead Yale J Biol Med
42329-349,1970
29
Fischer and Halstead Yale J Biol Med
42329-349,1970
30
DHF AT BANGKOK CHILDRENS HOSPITAL
31
EFFECT OF AVERAGE FORCE OF INFECTION (Ro) ON AGE
SPECIFIC SECONDARY INFECTION INCIDENCE
Ro 30 Ro 20 Ro 10
32
Dengue hemorrhagic fever/dengue shock syndrome
has occurred in some (but not all) dengue
epidemics since the 1950s,Why?
33
DHF does not occur if antibodies from first
infection neutralize the second infecting virus.
34
BANGKOK STUDYKliks et al AJTMH 40444, 1989.
  • 40 Bangkok school children had documented
    secondary DEN 2 infections (pre-infection blood
    sample contained dengue antibodies).
  • 7 were hospitalized 33 silent.
  • Undiluted pre-infection sera tested for
    neutralization or enhancement in human PBL
    cultures.

35
ADE AND DHF BLOCKED BY NEUTRALIZING ANTIBODIES
36
ANTIGENIC STRUCTURE OF VIRUS IQUITOS STUDY
  • School children cohorts followed from 1990 until
    now.
  • DEN 1 transmitted in 1990 - 1994.
  • DEN 2 transmitted from 1995.
  • Prevalence of neutralizing antibodies measured in
    1993, 1994 and 1995 cohorts.
  • In 1995, secondary DEN 2 infection rate
    estimated at 60.5

37
NO DHF with Secondary DEN 2 (American genotype)
infections
  • Total population, 5 - 14 yrs-old 81,479.
  • Total 2ndary DEN 2 infections 49,266.
  • Estimated hospitalized DHF 887-10247.
  • Estimated deaths 18 - 204.
  • DHF cases observed 0
  • Watts DM et al Lancet 3541431-4, 1999

38
NEUTRALIZATION OF AMERICAN GENOTYPE DEN 2
VIRUSES by 34 DEN 1- IMMUNE HUMAN SERA
39
ONE-WAY CROSS 17 DENGUE 2-IMMUNE SERA DO NOT
NEUTRALIZE DENGUE-1 VIRUSES
40
American genotype dengue 2 viruses are
neutralized in vitro by human antibodies to
dengue 1
BUT dengue 1 antibodies do not prevent but may
down regulate dengue 2 infections
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