Lesson learned from the adult dengue case · •DHF is not significantly associated with second dengue infections •DHF is caused by virulent viruses •DHF results from an abnormal

Lesson learned from the adult dengue case

Awareness of adult dengue cases

Situation of adult dengue cases

Severity disease

Factors promoting DHF/DSS (severity disease)

WHO Guideline (WHO dengue classification)

WHO Guideline 1997

WHO Guideline 2009

Dengue vaccine



Severity disease



WHO Guideline 1997

WHO Guideline 2009

Dengue vaccine

0

50

100

150

200

250

300

350

400

2003 2004 2005 2006 2007

0-4 5-9 10-14 15-24 25-34 35+

Rate

per 100,000 Pop.

Reported Cases of D.H.F,Total(26,27,66) per 100,000 Population, by Age-group, Thailand,

2003 - 2007 Fig 2

< 15 yrs > 15 yrs

Prof. Terapong Tantawichien

2013 DENGUE CASES IN BANGKOK

750

1585

2371

2204

1941

1523

1260

953

717

559

387

294

150108

52 30 22 9 2 1

015030045060075090010501200135015001650180019502100225024002550270028503000

0-4

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-99 กลมอาย(ป)

จ านวนผปวย (คน)

ไขเลอดออก

Professor Usa Thisyakorn

DIFFERENCES IN DENGUE SEVERITY IN INFANTS, CHILDREN, AND ADULTS IN

A 3-YEAR HOSPITAL-BASED STUDY IN NICARAGUA

Samantha Nadia Hammond SN, et al., Am J Trop Med Hyg 2005

1. Antibody–dependent enhancement (ADE)

2. Immune complex mechanism

activate complement

3. Immune elimination mechanism

DENV-infected monocytes/macrophages

cytokines activate complement

Factors promoting DHF (severity disease)

Dengue virus

Genome : Positive single-stranded RNA ~ 11 kb

: Single open reading frame

: 3 structural proteins

: 7 nonstructural proteins

C prM E NS1 NS2a NS2b NS3 NS4a NS4b NS5

Structure proteins Nonstructure proteins

5' Cap 3'

67% Similarity

Immune Response to Dengue Infection

Common Ag 1º (homotypic Ab)

(heterotypic Ab)

Pathogenesis of DHF / DSS

Antibody–dependent enhancement (ADE)

Common Ag 1º (homotypic Ab)(heterotypic Ab)

2º Enhancing AbDHF ( 87 – 98 % = 2º )DSS ( 95 – 99 % = 2º )



Severity disease



WHO Guideline 1997

WHO Guideline 2009

Dengue vaccine

http://www.who.int/csr/resources/publications/dengue/012-23.pdf

http://www.denguevirusnet.com/guidelines/19-guidelines/42-who-dengue-guidelines-and-documents.html

WHO Guideline 1997

Fever, headache, retro-orbital pain, myalgias, arthralgias+/- Haemorrhagic manifestations

ThrombocytopeniaHaemoconcentration

Spontaneous Bleeding

Pulse Pressure 20 mmHgHypotension, cold clammyskin, restlessness

Profound shockUndetectable bloodpressure & pulse

Classic Dengue Fever

Grade I DHF

Grade II DHF

Grade III DHF

Grade IV DHF

DSS

1997 WHO dengue classification


CONTROVERSIES IN DENGUE PATHOGENESIS

• The 1997 WHO case definition is inadequate

• DHF is not significantly associated with second dengue infections

• DHF is caused by virulent viruses

• DHF results from an abnormal T cell response

• DHF results from dengue infection-induced autoimmunity

• DHF results from DENV-infected endothelial cellsPediatrics and International Child health 2012; 32: S5-9.

Who Guideline 2009

(RCPT 2013)

Who Guideline 2009



Severity disease



WHO Guideline 1997

WHO Guideline 2009

Dengue vaccine

Dengue Vaccines:Latest Developments and Future Directions

• Live attenuated virus

• Chimeric virus

• Inactivated virus

• Subunit

• DNA

• Vector

• Recombinant E proteins

• VLP basedThisyakorn U, Thisyakorn C. Ther Adv Vaccines 2014; 2: 3-9. Doi: 10.1177/2051013613507862

Wilder-Smith & Macary, Curr Inf Dis Rep 16, 404, 2014

Bulletin WHO 65, 189-195, 1987

(1928-2004)

Origins of the

CYD vaccines

• Mexico, Philippine, Brazil, Malaysia and

Indonesia

• Thailand

Dengue Vaccine: Thailand (MU), Australia, Japan

Acknowledgement


Prof. Terapong Tantawichien

This adult dengue case

Thank you

https://www.google.co.th/search?q=clinical+spect

rum+of+dengue+infection&biw=975&bih=557&so

urce=lnms&tbm=isch&sa=X&ved=0CAYQ_AUoA

WoVChMI0__D3NKdyQIV0L-

OCh2ygwe7#tbm=isch&q=clinical+spectrum+of+

dengue+infection+iceberg&imgrc=e83qIPTlUBI0GM%3A

Immune Response to Dengue Infection

Dengue NS 1 Ag

Clinical Spectrum of DENV Infection

Field’s Virology, 4th Ed. Chapter 9: Pathogenesis of Viral Infections, Kenneth L. Tyler and Neal Nathanson

DHF/Severe Dengue

Hospitalized DF

Non-hospitalized DF

Inapparent

DENV Infection

Lesson learned from the adult dengue case · •DHF is not significantly associated with second dengue infections •DHF is caused by virulent viruses •DHF results from an abnormal

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