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7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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
7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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
7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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
7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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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7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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.
7/27/2019 Ns1 Antigen Untuk Deteksi Dini Infeksi Virus Dengue Edh
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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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