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• Background

• DF/DHF high morbidity and mortality rate

• Endemic in at least 100 countries

• A major problem in the world, especialy intropical countries.

• Vector control is important, but is reality living

habitat of Aedes aegypti is difficult to control

• Late diagnosis is fatal• Mechanism factorr lead to severe dengue is

unknown

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•Over 50 million infections are reportedannually with 250.000-500.000 DHF.

• Caused by 4 serotype of dengue viruses

(Den 1, Den 2, Den 3, Den 4)

•No antiviral available

• No vaccine available

• WHO. Geneva 2003

• Kumarasamy et al. Singapore Med J 2007;48:669-73

• Alcon et al. J Clin Microbiol 2002; 40:378-81

• Lindergend et al. J.Microbiol 2005;43:2850-55

• Lolekha R et al.J Trop. Med. Public Health

2004;35:391-5

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NON STRUCTURAL

PROTEINFUNCTION

• NS1

• NS2A

• NS2B

• NS3

• NS4A

• NS4B

• NS5

Replication

Unknown

Cofactor NS3, connection on 3 NCR, NS3 and NS5

Protease Serin and NTPase helikase

Replication

Unknown

Unknown

Replication RNA with NS3

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STRUCTURAL

PROTEINFUNCTION

• Core

• Pre M

• M protein

•E Protein

Nucleocapsid protein

Glycoprotein precussor 

Host cell fussion

 Assembling of viruses

Glycoprotein membrane

Host cell fussion of virus

Glycoprotein envelopeRespon immune induction

 Antibody reseptor connection

Sophie A et al. J Virol 2005;79:11403-11.

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Serotype Number of sera Sensitivity of dengue NS1 Ag (95%

CI)

• Den 1

• Den 2

• Den 3

• Den 4

93

31

24

29

88,9%(65,8%-94,8%)

87,1%(70,1%-96,3%)

100%(85,6%-100%)

93,3%(77,9%-97,9%)

• Philippe D et al. Clin and Vaccine 2006; 13:1185-89

• Alcon S et al. J Clin. Microbiol 2002; 40:378-81

• Chou-Feng et al.J Virol 2005;79:11403-11

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Serotype No.of sera test No(+) NS1 Ag test Sensitivity (%) 95% CI

• Den 1

• Den 2

• Den 3

• Den 4

• All

serotype

42

42

107

48

239

38

37

94

43

212

90,5

88.1

87.9

89.6

88.7

77,4-97.3

77.4-96

80.1-93.4

77.3-96.5

84-92.4

Chung Yi L et al. Am J Trop Med Hyg 2003;32:164-69

Paul R et al. J Clin Microbiol 2000;38:1053-57.

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Day after 

begining of fever 

Number of sera Sensitivity of Dengue

NS1 antigen (%)

Sensitivity of Dengue

IgM ELISA(%)

0

1

2

34

5

≥6 

10

33

40

2027

19

28

100

87.8

92.5

9596.3

52.6

35.7

0

5.1

6.1

1548.1

94.1

100

• Paul R et al. J Clin Microbiol 2000;38:1053-57

• Pei Yun S et al. Clin and Diags Laboratory

Immunol 2003;10:622-30

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Diagnostic methode Number of serum samples tested positive 

Primary Dengue (NS1) Secondary Dengue

(NS1)

Combined (NS1)

• Viral isolation alone

• RT-PCR

• Viral isolation + RT-PCR

• Serology (pair sera)

• Total

64(62)

48(45)

72(72)

8(8)

192(187)

7(6)

20(12)

2(2)

3(2)

32(22)

71(68)

68(57)

74(74)

11(10)

224(209)

• Alcon S et al. J Clin Microbiol 2002;40:378-81

• Shu P et al. Clin Diags Laboratory Immunol

2004;11:642-50.

• Pei Yun S et al.Clin Diags and Laboratory

Immunol 2003;10:622-30.

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Diagnostic methode Number of serum samples tested positive

Primary dengue

(NS1)

Secondary

dengue (NS1)

Combined (NS1)

• Viral isolation alone

• RT  – PCR

• Viral isolation+RT-PCR

• Serology(pair sera)

• Total

29(28)

13(12)

18(18)

8(8)

68(66)

5(4)

12(6)

0(0)

3(2)

20(12)

34(32)

25(18)

18(18)

11(10)

88(78)

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Diagnostic methode Number of serum samples tested positive

Primary dengue

(NS1)

Secondary

dengue (NS1)

Combined (NS1)

• Viral isolation alone

• RT  – PCR

• Viral isolation+RT-PCR

• Serology(pair sera)

• Total

35(34)

35(33)

54(54)

0(0)

124(121)

2(2)

8(6)

2(2)

0(0)

12(10)

37(36)

43(39)

56(56)

0(0)

136(131)

• Eric M et al. Am J Trop Med Hyg 2003;32:164-69

• Darfu et al. Clin Chemistry 2006;52:1486-91

• Lindergend G et al 2005; 43:2850-5

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Day of 

fever 

No. Sera

of tested

Dengue NS1 Antigen Test MAC ELISA

No. (+) test Sensitvity(%)

95% CI No. (+)Elisa

Sensitivity(%)

95% CI

0

1

2

3

4

5

6

≥7 

Total

15

70

59

40

25

19

18

20

266

15

61

54

34

19

8

17

9

217

100

87.1

91.5

85

76

42.1

94.4

45

81.6

78.2-100

77-93.9

81.3-97.2

70.2-94.3

54.9-90.6

20.3-66.5

75.7-99.8

23.1-68.5

76.4-86.1

0

1

3

6

8

16

18

20

72

0

1.4

5.1

15

32

84.2

100

100

26.7

0.0-23.2

0-7.6

1.1-14.2

5.7-29.8

15-53.5

60.4-96.6

81-100

83.1-100

21.8-32.8

• Kumarasamy V et al. Singapore Med J 2007;48:669-73

• Pei Yun S et al. Clin Diags and laboratory Immunol

2003;10:622-30

• Pei YS et al. J Clin Microbiol 2002; 40:1840-44.

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• Dengue is endemic desease affecting tropical and

subtropical region.

• Infections with dengue virus causes a broad spectrum

of illnesses.

•

Early detection and management is important• Prompt diagnosis of dengue infection is imperative in

the control of dengue virus infection and management

of patient.

• Detection nonstructural protein NS1 antigen analternative methode for early diagnosis.

• Sensitivity 88%-100% and spesificity 100%.

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