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

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...

Documents

Transcript of Lesson learned from the adult dengue case · •DHF is not significantly associated with second...