Power Point File Present by Dr Wilsom Lam QEH (Updated 030603pm)

8/6/2019 Power Point File Present by Dr Wilsom Lam QEH (Updated 030603pm)

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Dengue Fever

Epidemiology and the Viruses

Dr Wilson LamDivision of Infectious Diseases

Department of Medicine QEH

3 June 2003


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Dengue fever

Dengue historyThe viruses and the vector

Transmission of viruses

Epidemiology Global Southeast Asia Hong Kong

Epidemiological features DF DHF/DSS

Reimmergence of dengue fever


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Historical background

Dengue like illness date back to more

than 200 years ago

1779-1780 in Asia, Africa and NorthAmerica

Viral etiology established by the 1940s

Global pandemic in Southeast Asiaafter World War II


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Dengue viruses

SS-RNA arbovirus (Flavivirus)

4 serotypes (DEN-1, 2, 3, 4) Based on envelop glycoprotein DEN-1 and 3 are more closely related DEN-4 less closely related to others Virulent variants (genotypes) within serotype

Infection with any serotype confers specificlifelong immunity

Transient cross-protection to other serotypes

Any serotype can cause severe / fatal disease


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Mosquito vectors

All known vectors belong to genusAedes

Vector competence and vectorial capacity of

different species vary Different species

Different geographic populations of the same

species

No correlation between clinical features ofsubsequent disease


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Mosquito vectors

Subgenus Stegomyia contains the most

important vectors of dengue virusesAe. aegypti, Ae. albopictus and Ae. polynesiensis

Ae. aegypti African origin

Not found in Hong Kong

Most important vectors worldwide Linked with human activities such as uncontrolled

urbanization, deterioration of urban environment

and decreasing standard of sanitation


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Ae. Albopictus (1)

Asian species South-East Asia, China, Japan, Indonesia, islands in the

Indian Ocean, Hawaii

Spreading to the United States, South America, Africa, the

Pacific and south of europe

Originally a forest mosquito feeding on a variety of

animals and breeding in tree holes

Become adapted to human environment

Natural containers such as tree holes, plant axils, cutbamboo stumps and opened coconuts

Outdoor artificial containers such as water storage

barrels and trash receptacles


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Ae. Albopictus (2)

Can persist as far north as Beijing orChicago (average isotherm of 0C)

Optimal growth at 25 C to 30CEggs can resist desiccation for severalmonths

10 days for egg-larva-purpa-adult cycleAe. albopictus females known tosurvive for up to 122 days (daily

mortalities 8-15%)


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Ae. Albopictus (3)

Density much influenced by rainfallFeed outdoors during daytime

Peak at 8-9 a.m. & 5-6 p.m.

Multiple bites per feedActive maximum dispersal range offemales about 400 to 600m

Passive dispersal less important


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Incubation

Period:

3-14 days

Viraemia & Fever: 5-7 days

Vector

Humidity:

Rainfall & Temp.

Susceptible hosts,

(population)

Source patients

ExtrinsicIncubation Period:

1-2 weeks


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Extrinsic incubation period 10 to 14 days Depends on

Ambient temperature

Humidity Viraemic level in the human host Virus strains

Intrinsic incubation period

4 to 7 days (Range 3-14 days) Viraemia may exist for 6 to 18 hours before onsetof symptoms

Symptomatic viraemic period is 4 to 5 days (up to12 days)


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At Risk Population: 2500 million

Dengue cases / Yr.: 50 million (DHF: 500 000)

Brazil 2001: 390,000 cases (670 DHF)

Dengue fever endemic regions


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Dengue in Southeast Asia

WHO 2001


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Stratification of DF/DHF in

South-East Asia Region Category B (Bangladesh,

India, Maldives, Sri Lanka) DHF is an emergent disease

Cyclical epidemics are

becoming more frequent Multiple virus serotypes

circulating

Expanding geographically

within countries

Aedes aegyptiis theprincipal epidemic vector

Role ofAedes albopictus is

uncertain

Category A (Indonesia,Myanmar, Thailand)

Major public health problemLeading cause of hospitalization

and death among childrenCyclical epidemics in urbancentres with 3-5 year periodicitySpreading to rural areasMultiple virus serotypes circulatingAedes aegyptiis the principalepidemic vectorRole ofAedes albopictus isuncertain


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DF Macau

1,502 cases in 2001 mostly indigenous First 14 cases reported in late August 2001

Last case in December

All were minor cases without complications

Origin and cause unknown

Mostly serotype DEN-2 (2 cases of DEN-1)

Up to end September 2002 Only 1 imported case (Thailand)


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0

2

4

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8

10

12

14

1618

Jan02

Feb02

Mar02

Apr02

M

ay02

Jun02

Jul02

A

ug02

Sep02

Oct02

Nov02

Dec02

Local

Imported

DF Hong Kong 2002


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0

1

2

3

4

5

6

15 to 28

July

29 Jul to

11 Aug

12 to 25

Aug

26 Aug to

8 Sep

9 to 22

Sep

23 Sep to

6 Oct

NonMaWan

MaWanrelated

DF Hong Kong 2002


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Dengue in Hong Kong

From 1994 to 2001, inclusive Cases: DF (68), DHF (4)

All were imported cases

Peak incidence at September (?return from travel)

2002 (up to 19 October) 20 indigenous cases

all DF, aged 20 to 72 yrs., Male: 13

16 cases related to Ma Wan (6 residents, 10 CSW)

onset: early July to 25 September All except one, were DEN-1

index case was suspected on 19 Sep. 2002

HK strains were different phylogenetically from Macau

strains.


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0

2

4

6

8

10

12

14

1618

Jan03

Feb03

Mar03

Apr03

M

ay03

Local

Imported

DF Hong Kong 2003


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Epidemiological features

Dengue fever (DF)

Dengue haemorrhagic fever (DHF) and

dengue shock syndrome (DSS)

DHF is not DF with haemorrhagic features


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DF epidemiology

Spread Endemic or epidemic

Travel along transportation routes

First appears in seaport and airport cities


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DF epidemiology

Seasonality Usually rainy seasons

Vectors, such asAe. albopictus, that have outdoor larvalhabitats more affected by rainfall

High humidity Longer mosquito survival

High temperature Vector distribution

Adult longevity Shorter extrinsic incubation period Smaller females more blood meals

Water cooler recirculation troughs during dryseasons


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DF epidemiology

Severity Vary in rate of transmission, percentage of

population involved and clinical severity

Age Pre-adolescent children less severe

Nearly all adults overt illness

Immune status Highly immune population less reported disease


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DF epidemiology

Severity Ethnicity

Strain variation Disease severity and haemorrhagic phenomenon vary

from outbreak to outbreak

Unique serotype or viral strain-specific factors

Level of circulating viruses


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DF epidemiology

Age/sex Mostly adults

Adult women and pre-school children in some

outbreaks

Transmission by daytime-biting


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Dengue Hemorrhagic Fever

(DHF)

Fever, or recent history of acute fever

Hemorrhagic manifestations (grade I & II)Low platelet count ( 100,000/mm3)

Objective evidence of leaky capillaries:

elevated hematocrit (

20% over baseline) low albumin / hypoproteinaemia

pleural or other effusions

4 Necessary Criteria (WHO):4 Necessary Criteria (WHO):

First recognized in the Philippines in 1953


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Dengue Shock Syndrome (DSS)

4 criteria for DHF

Evidence of circulatory failure:Rapid and weak pulseNarrow pulse pressure ( 20 mm Hg) OR

hypotension for age

Cold, clammy skin/altered mental status(grade III)

or profound Shock (grade IV)


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DHF/DSS epidemiology

Early reports 1897 Northern Australia 1928 Greece

1935 Taiwan 1950 Thailand mid-1980s Southern China and Hainan Island

Asian DHF/DSS epidemics Multiple types of dengue viruses simultaneously or

sequentially endemic Secondary-type antibody responses observed Only during secondary dengue infections


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Infection parity and enhancing

antibodies

Secondary-type dengue infectionsPrimary in infants born to dengue-immune

mothers

Antigens shared between first and second

infecting serotypes

Shift the spectrum towards more severe

disease


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Pathogenesis of antibody dependent

enhancement Serum antibodies developed can neutralize

dengue virus of that same serotype (homologous)

Pre-existing heterologous antibodies form

complexes but no neutralization

Infected monocytes release vasoactive mediators Increased vascular permeability

Haemorrhagic manifestations


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Protective antibodiesLow levels of cross-reactvie neutralizing

antibody protect against DHF/DSSDifferent viral antigens?

Epitopes closely similar to serotype-specific

neutralizing epitopes of another virus

Different host response?Human immune system responds differently to

a single specific repertoire


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Viral strainSeverity

Viruses which causes mild and severe diseaseappear genetically identical

Occurrence or non-occurrenceOnly dengue viruses of Asian origins at

epidemic proportionDistribution of heterotypic and non-heterotypic

antigens


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Age Greatest susceptibility to shock is 8 to 10 years

? Capillaries of of children more prone to cytokine-

mediated increased permeability

Sex Shock cases and deaths more frequently in female

than in male children

? Immune responses of females more competent

? Capillary bed of females more prone to

increased capillary permeability


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Nutritional statusModerate to severe protein-calorie

malnutrition reduces risk to DHF/DSS indengue infected children

Malnutrition suppresses cellular immune

responses

Preceding host conditionsPeptic ulcer and menstrual periods risk

factors for severe bleeding


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Reemergence of DF/DHF

Unprecedented human population growth

Unplanned and uncontrolled urbanization

Inadequate waste management and watersupply

Increased distribution and densities of vector

mosquitoes

Lack of effective mosquito control

Increased movement and spread of dengue

viruses


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Dengue Fever: Case Definition

For Epidemiological Purposes:

Suspected case: An acute febrile illness characterized by intense

headache, retro-orbital pain, myalgia, arthralgia,

rash, leucopenia or haemorrhagic manifestations.

Probable case: A clinically compatible case withsupportive serology.

Confirmed case: A clinically compatible case withlaboratory confirmation.


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Supportive serologic findings:An antibody titer of1280ora positive IgM antibody test

on a single serum sample to Dengueantigen.

Criteria for laboratory confirmation: ( one)

Isolation of Dengue virus from patient samples; A 4x change in antibody titers to Dengue

antigens in paired serum samples; Detection of Dengue virus genomic sequences

patient samples by PCR.

Laboratory support for case

definition

S l i l P fil


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Serological Profile

Dengue IgMMean Max. Temperature Virus

Vaughn et al., J Infect Dis, 1997; 176:322-30.

Fever Day

0

20

40

60

80

100

P

erce

ntVirusPo

sitive

-4 -3 -2 -1 0 1 2 3 4 5 6

39.5

39.0

38.538.0

37.5

37.0Tem

perature(de

greesCelsiu

s)

D

engu

eIgM (

EIAunit

s)300

150

0

75

225

Primary Infection: IgM>IgG

Secondary Infection: IgG>IgM

viraemia


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Virological Diagnosis

Dengue-specific testsVirus isolationSerology

HAI IgM

Immunochromatographic IgM EIA

Real Time - PCR

Rapid Strip Test: False


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Rapid Strip Test: FalsePositives

BOOK K M

EBV IgM +ve

Samples tested 744

False +ve 26

Specificity 96.5%

* information from GVU, DH on 19 October 2002

Sequential testing or confirmation isrequired.


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Ovitrap index

Ovitrapblack container, with rough surface, waterplaced 1m above the ground, 100m apart50 traps in an area of 0.5 km2 incubate for 1 week at 25C

Index the % of trap showingAedes albopictus

larva reflects the extent (but not the density) of

infestation.


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Ovitrap in hospital area


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Sing Pao 20 Oct 2002

Press Release FEHD December 21, 2002

Ovitrap index in Hong Kong

0

5

10

15

20

25

30

35

July

August

September

October

November

December

Ovitra

2001

2002


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Control of Dengue Fever

Statutory Notification since 1994

Laboratory surveillance

Active case finding

Self-reporting (DH hotline: 2961 8966)

Global surveillance

Case investigation Information dissemination


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Control of Dengue Fever

Case investigation

confirm diagnosis

travel history

local movement

potential mosquito breeding sites

S/S among travel & local collaterals medical surveillance of collaterals


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Power Point File Present by Dr Wilsom Lam QEH (Updated 030603pm)

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